rs771863463

chr10-69005082-C-A

Variant summary

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

The NM_015634.4(KIFBP):c.562C>A(p.Leu188Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIFBP NM_015634.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.80

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=0.114057004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIFBP	NM_015634.4	c.562C>A	p.Leu188Ile	missense_variant	3/7	ENST00000361983.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIFBP	ENST00000361983.7	c.562C>A	p.Leu188Ile	missense_variant	3/7	1	NM_015634.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251358 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135862

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 6.84e-7 AC: 1 AN: 1461380 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 727044

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 15, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	21
Dann	Uncertain	0.98
DEOGEN2	Benign	0.060	T;T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	0.67	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.48	N;.;.
REVEL	Benign	0.064
Sift	Benign	0.23	T;.;.
Sift4G	Benign	0.21	T;.;T
Polyphen		0.54	P;.;.
Vest4		0.29
MutPred		0.18		Gain of methylation at K193 (P = 0.0559);.;Gain of methylation at K193 (P = 0.0559);
MVP		0.45
MPC		0.65
ClinPred		0.40	T
GERP RS		4.9
Varity_R		0.049
gMVP		0.063

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: rs771863463; hg19: chr10-70764838;