rs148768851

chr10-68988900-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015634.4(KIFBP):c.68A>G(p.Glu23Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00122 in 1,614,230 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00072 (13 hom.)
• Consequence: KIFBP NM_015634.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:7
• Conservation: PhyloP100: 7.05

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006440878).
• BP6: Variant 10-68988900-A-G is Benign according to our data. Variant chr10-68988900-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 158698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00605 (922/152352) while in subpopulation AFR AF= 0.0212 (882/41590). AF 95% confidence interval is 0.02. There are 8 homozygotes in gnomad4. There are 417 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIFBP	NM_015634.4	c.68A>G	p.Glu23Gly	missense_variant	1/7	ENST00000361983.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIFBP	ENST00000361983.7	c.68A>G	p.Glu23Gly	missense_variant	1/7	1	NM_015634.4	P1

Frequencies

GnomAD3 genomes AF: 0.00605 AC: 921 AN: 152234 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00178 AC: 446 AN: 251208 Hom.: 2 AF XY: 0.00132 AC XY: 180 AN XY: 135862

Gnomad AFR exome AF: 0.0235

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.000979

GnomAD4 exome AF: 0.000720 AC: 1052 AN: 1461878 Hom.: 13 Cov.: 30 AF XY: 0.000645 AC XY: 469 AN XY: 727244

Gnomad4 AFR exome AF: 0.0234

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000980

Gnomad4 OTH exome AF: 0.00154

GnomAD4 genome AF: 0.00605 AC: 922 AN: 152352 Hom.: 8 Cov.: 33 AF XY: 0.00560 AC XY: 417 AN XY: 74490

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00113 Hom.: 0

Bravo AF: 0.00705

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0213 AC: 94

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00213 AC: 259

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1 Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Goldberg-Shprintzen syndrome Uncertain:1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 12, 2021	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics, Erasmus University Medical Center	May 16, 2019	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 17, 2016	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	KIFBP: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 13, 2023	- -

KIFBP-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 26, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T;T;T
MetaRNN	Benign	0.0064	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.1	D;.;.
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D;.;.
Sift4G	Uncertain	0.0090	D;.;D
Polyphen		1.0	D;.;.
Vest4		0.38
MVP		0.68
MPC		1.4
ClinPred		0.019	T
GERP RS		5.7
Varity_R		0.69
gMVP		0.75

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

Other links and lift over

dbSNP: rs148768851; hg19: chr10-70748656;