Variant 11-1608103-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001012708.2(KRTAP5-3):c.283G>A(p.Val95Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,578,802 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000058 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

KRTAP5-3
NM_001012708.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.05

Variant links:

Genes affected

KRTAP5-3 (HGNC:23598): (keratin associated protein 5-3) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034679413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-3	NM_001012708.2 linkuse as main transcript	c.283G>A	p.Val95Ile	missense_variant	1/1	ENST00000399685.1	NP_001012726.1	Q6L8H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-3	ENST00000399685.1 linkuse as main transcript	c.283G>A	p.Val95Ile	missense_variant	1/1	6	NM_001012708.2	ENSP00000382592.1		Q6L8H2

Frequencies

GnomAD3 genomes

AF:

0.0000578

AC:

AN:

138440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000190

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000728

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250120

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.000193

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1440362

Hom.:

Cov.:

101

AF XY:

0.00000418

AC XY:

AN XY:

717092

show subpopulations

Gnomad4 AFR exome

AF:

0.000247

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:

0.0000189

Gnomad4 NFE exome

AF:

0.00000728

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.0000578

AC:

AN:

138440

Hom.:

Cov.:

AF XY:

0.0000748

AC XY:

AN XY:

66812

show subpopulations

Gnomad4 AFR

AF:

0.000190

Gnomad4 AMR

AF:

0.0000728

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.283G>A (p.V95I) alteration is located in exon 1 (coding exon 1) of the KRTAP5-3 gene. This alteration results from a G to A substitution at nucleotide position 283, causing the valine (V) at amino acid position 95 to be replaced by an isoleucine (I). 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

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.61

DANN

Benign

0.55

DEOGEN2

Benign

0.0039

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0018

M_CAP

Benign

0.00063

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

PROVEAN

Benign

-0.42

REVEL

Benign

0.028

Sift

Benign

0.23

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.036

MVP

0.014

MPC

0.020

ClinPred

0.037

GERP RS

-3.1

Varity_R

0.027

gMVP

0.0098

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