rs553587755

chr10-68988861-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015634.4(KIFBP):c.29G>T(p.Cys10Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,614,274 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: KIFBP NM_015634.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 7.66

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11991057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIFBP	NM_015634.4	c.29G>T	p.Cys10Phe	missense_variant	1/7	ENST00000361983.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIFBP	ENST00000361983.7	c.29G>T	p.Cys10Phe	missense_variant	1/7	1	NM_015634.4	P1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152270 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.0000239 AC: 6 AN: 251162 Hom.: 0 AF XY: 0.0000294 AC XY: 4 AN XY: 135880

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461886 Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152388 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74518

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000200

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 10, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Ambry Genetics	Jun 11, 2021	The c.29G>T (p.C10F) alteration is located in exon 1 (coding exon 1) of the KIF1BP gene. This alteration results from a G to T substitution at nucleotide position 29, causing the cysteine (C) at amino acid position 10 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.45
Cadd	Uncertain	23
Dann	Benign	0.97
DEOGEN2	Benign	0.083	T;T;T
Eigen	Benign	-0.067
Eigen_PC	Benign	0.058
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.9	N;.;.
REVEL	Benign	0.12
Sift	Benign	0.092	T;.;.
Sift4G	Benign	0.081	T;.;D
Polyphen		0.046	B;.;.
Vest4		0.20
MutPred		0.46		Gain of methylation at K12 (P = 0.0902);Gain of methylation at K12 (P = 0.0902);Gain of methylation at K12 (P = 0.0902);
MVP		0.52
MPC		0.71
ClinPred		0.83	D
GERP RS		3.9
Varity_R		0.43
gMVP		0.45

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: rs553587755; hg19: chr10-70748617;