Variant chr11-71565705-T-A 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_001012710.2(KRTAP5-10):c.118T>A(p.Ser40Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,610,386 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00020 ( 1 hom., cov: 25)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

KRTAP5-10
NM_001012710.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.209

Variant links:

Genes affected

KRTAP5-10 (HGNC:23605): (keratin associated protein 5-10) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-10 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=0.026068032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-10	NM_001012710.2 linkuse as main transcript	c.118T>A	p.Ser40Thr	missense_variant	1/1	ENST00000398531.3	NP_001012728.1	Q6L8G5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-10	ENST00000398531.3 linkuse as main transcript	c.118T>A	p.Ser40Thr	missense_variant	1/1	6	NM_001012710.2	ENSP00000381542.1		Q6L8G5

Frequencies

GnomAD3 genomes

AF:

0.000199

AC:

AN:

150682

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000710

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

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:

0.0000601

AC:

AN:

249522

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.000835

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:

0.0000349

AC:

AN:

1459590

Hom.:

Cov.:

121

AF XY:

0.0000289

AC XY:

AN XY:

726088

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000199

AC:

AN:

150796

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

73646

show subpopulations

Gnomad4 AFR

AF:

0.000708

Gnomad4 AMR

AF:

0.0000661

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:

0.000253

Hom.:

ESP6500AA

AF:

0.000687

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000280

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

Oct 02, 2023

The c.118T>A (p.S40T) alteration is located in exon 1 (coding exon 1) of the KRTAP5-10 gene. This alteration results from a T to A substitution at nucleotide position 118, causing the serine (S) at amino acid position 40 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.088

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.15

M_CAP

Benign

0.00093

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PROVEAN

Benign

-0.41

REVEL

Benign

0.068

Sift

Pathogenic

0.0

Sift4G

Benign

0.22

Polyphen

0.62

Vest4

0.17

MVP

0.014

MPC

0.0086

ClinPred

0.043

GERP RS

1.8

Varity_R

0.15

gMVP

0.038

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