rs62625033

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015634.4(KIFBP):c.518T>C(p.Met173Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00786 in 1,584,916 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 66 hom. )

Consequence

KIFBP
NM_015634.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 6.47

Variant links:

Genes affected

KIFBP (HGNC:23419): (kinesin family binding protein) This gene encodes a kinesin family member 1 binding protein that is characterized by two tetratrico peptide repeats. The encoded protein localizes to the mitochondria and may be involved in regulating transport of the mitochondria. Mutations in this gene are associated with Goldberg-Shprintzen megacolon syndrome. [provided by RefSeq, Mar 2010]

KIFBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008571029).

BP6

Variant 10-69000515-T-C is Benign according to our data. Variant chr10-69000515-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 158697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-69000515-T-C is described in Lovd as [Benign]. Variant chr10-69000515-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00605 (922/152336) while in subpopulation NFE AF= 0.00989 (673/68026). AF 95% confidence interval is 0.00927. There are 1 homozygotes in gnomad4. There are 394 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 66 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFBP	NM_015634.4 link	c.518T>C	p.Met173Thr	missense_variant	Exon 2 of 7	ENST00000361983.7	NP_056449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFBP	ENST00000361983.7 link	c.518T>C	p.Met173Thr	missense_variant	Exon 2 of 7	1	NM_015634.4	ENSP00000354848.4		Q96EK5

Frequencies

GnomAD3 genomes

AF:

0.00606

AC:

923

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00989

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00650

AC:

1632

AN:

251074

Hom.:

AF XY:

0.00669

AC XY:

908

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00509

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00467

Gnomad FIN exome

AF:

0.00246

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00735

GnomAD4 exome

AF:

0.00806

AC:

11542

AN:

1432580

Hom.:

Cov.:

AF XY:

0.00800

AC XY:

5720

AN XY:

714664

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00499

Gnomad4 ASJ exome

AF:

0.00586

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00528

Gnomad4 FIN exome

AF:

0.00308

Gnomad4 NFE exome

AF:

0.00917

Gnomad4 OTH exome

AF:

0.00840

GnomAD4 genome

AF:

0.00605

AC:

922

AN:

152336

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

394

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00540

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00989

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00877

Hom.:

Bravo

AF:

0.00578

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00919

AC:

ExAC

AF:

0.00661

AC:

803

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Aug 08, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jun 15, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:5

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 19, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KIFBP: BS2 -

May 28, 2019

Mendelics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

KIFBP-related disorder

Benign:1

Sep 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Goldberg-Shprintzen syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.063

T;T;T

Eigen

Benign

-0.059

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0086

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.0

N;.;.

REVEL

Benign

0.13

Sift

Benign

0.71

T;.;.

Sift4G

Benign

0.30

T;.;T

Polyphen

0.16

B;.;.

Vest4

0.77

MVP

0.48

MPC

0.54

ClinPred

0.019

GERP RS

5.1

Varity_R

0.28

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over