rs35893997

Variant names:

• chr10-69016203-C-T
• rs35893997
• NM_015634.4:c.1653C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015634.4(KIFBP):​c.1653C>T​(p.Ala551Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 1,612,732 control chromosomes in the GnomAD database, including 3,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (235 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3392 hom.)
• Consequence: KIFBP NM_015634.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0810
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• Goldberg-Shprintzen syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 10-69016203-C-T is Benign according to our data. Variant chr10-69016203-C-T is described in ClinVar as Benign. ClinVar VariationId is 158694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.081 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFBP	NM_015634.4	c.1653C>T	p.Ala551Ala	synonymous_variant	Exon 7 of 7	ENST00000361983.7	NP_056449.1
KIFBP	XM_017016067.2	c.855C>T	p.Ala285Ala	synonymous_variant	Exon 4 of 4		XP_016871556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFBP	ENST00000361983.7	c.1653C>T	p.Ala551Ala	synonymous_variant	Exon 7 of 7	1	NM_015634.4	ENSP00000354848.4

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7526 AN: 152092 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0735

Gnomad OTH AF: 0.0771

GnomAD2 exomes AF: 0.0504 AC: 12615 AN: 250286 AF XY: 0.0513

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.0448

Gnomad ASJ exome AF: 0.0996

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0296

Gnomad NFE exome AF: 0.0722

Gnomad OTH exome AF: 0.0677

GnomAD4 exome AF: 0.0644 AC: 94058 AN: 1460522 Hom.: 3392 Cov.: 33 AF XY: 0.0633 AC XY: 45980 AN XY: 726462

African (AFR) AF: 0.0117 AC: 390 AN: 33390

American (AMR) AF: 0.0473 AC: 2104 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 2525 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0218 AC: 1876 AN: 86004

European-Finnish (FIN) AF: 0.0302 AC: 1615 AN: 53406

Middle Eastern (MID) AF: 0.120 AC: 692 AN: 5756

European-Non Finnish (NFE) AF: 0.0727 AC: 80847 AN: 1111354

Other (OTH) AF: 0.0665 AC: 4009 AN: 60308

GnomAD4 genome AF: 0.0494 AC: 7515 AN: 152210 Hom.: 235 Cov.: 32 AF XY: 0.0468 AC XY: 3485 AN XY: 74424

African (AFR) AF: 0.0133 AC: 552 AN: 41530

American (AMR) AF: 0.0659 AC: 1007 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4820

European-Finnish (FIN) AF: 0.0258 AC: 273 AN: 10590

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0735 AC: 4998 AN: 68014

Other (OTH) AF: 0.0768 AC: 162 AN: 2110

Alfa AF: 0.0582 Hom.: 226

Bravo AF: 0.0515

Asia WGS AF: 0.0190 AC: 66 AN: 3478

EpiCase AF: 0.0880

EpiControl AF: 0.0856

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 23, 2016

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Goldberg-Shprintzen syndrome Benign:3

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. -

Sep 21, 2015

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

May 07, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.4
DANN	Benign	0.64
PhyloP100		-0.081
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35893997; hg19: chr10-70775959;