Variant chr11-71565952-G-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_001012710.2(KRTAP5-10):c.365G>T(p.Gly122Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000643 in 1,556,218 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: 𝑓 0.000014 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

KRTAP5-10
NM_001012710.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

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=0.061288953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-10	NM_001012710.2 linkuse as main transcript	c.365G>T	p.Gly122Val	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.365G>T	p.Gly122Val	missense_variant	1/1	6	NM_001012710.2	ENSP00000381542.1		Q6L8G5

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

147732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000402

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:

0.00000401

AC:

AN:

249422

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135014

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000568

AC:

AN:

1408486

Hom.:

Cov.:

AF XY:

0.00000572

AC XY:

AN XY:

699348

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000247

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:

0.000122

GnomAD4 genome

AF:

0.0000135

AC:

AN:

147732

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

72084

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000402

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000659

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

Apr 29, 2024

The c.365G>T (p.G122V) alteration is located in exon 1 (coding exon 1) of the KRTAP5-10 gene. This alteration results from a G to T substitution at nucleotide position 365, causing the glycine (G) at amino acid position 122 to be replaced by a valine (V). 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

0.25

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0038

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.38

M_CAP

Benign

0.00079

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

3.0

PROVEAN

Benign

-1.3

REVEL

Benign

0.037

Sift

Uncertain

0.024

Sift4G

Benign

0.15

Polyphen

0.41

Vest4

0.18

MutPred

0.20

Loss of glycosylation at K121 (P = 0.1452);

MVP

0.14

MPC

0.0082

ClinPred

0.098

GERP RS

-0.23

Varity_R

0.041

gMVP

0.021

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