Variant 11-1585096-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001005922.1(KRTAP5-1):c.154G>A(p.Val52Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000771 in 1,542,508 control chromosomes in the GnomAD database, including 4 homozygotes. 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 0.00018 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000068 ( 4 hom. )

Consequence

KRTAP5-1
NM_001005922.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.157

Variant links:

Genes affected

KRTAP5-1 (HGNC:23596): (keratin associated protein 5-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-1 links:

KRTAP5-AS1 (HGNC:27877): (KRTAP5-1/KRTAP5-2 antisense RNA 1)

KRTAP5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09637895).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-1	NM_001005922.1 linkuse as main transcript	c.154G>A	p.Val52Met	missense_variant	1/1	ENST00000382171.2	NP_001005922.1
KRTAP5-AS1	NR_021489.2 linkuse as main transcript	n.328+12028C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-1	ENST00000382171.2 linkuse as main transcript	c.154G>A	p.Val52Met	missense_variant	1/1		NM_001005922.1	ENSP00000371606	P1
KRTAP5-AS1	ENST00000424148.1 linkuse as main transcript	n.328+12028C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000175

AC:

AN:

126032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000243

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000247

Gnomad SAS

AF:

0.000525

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000132

AC:

AN:

241878

Hom.:

AF XY:

0.000145

AC XY:

AN XY:

131036

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.0000930

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000689

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000678

AC:

AN:

1416372

Hom.:

Cov.:

AF XY:

0.0000979

AC XY:

AN XY:

704780

show subpopulations

Gnomad4 AFR exome

AF:

0.000444

Gnomad4 AMR exome

AF:

0.000101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000771

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000460

Gnomad4 OTH exome

AF:

0.000122

GnomAD4 genome

AF:

0.000182

AC:

AN:

126136

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

61312

show subpopulations

Gnomad4 AFR

AF:

0.000513

Gnomad4 AMR

AF:

0.000242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000248

Gnomad4 SAS

AF:

0.000526

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000921

Hom.:

ExAC

AF:

0.000165

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

Jun 16, 2024

The c.154G>A (p.V52M) alteration is located in exon 1 (coding exon 1) of the KRTAP5-1 gene. This alteration results from a G to A substitution at nucleotide position 154, causing the valine (V) at amino acid position 52 to be replaced by a methionine (M). 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

0.24

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.021

Eigen

Benign

0.019

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.13

M_CAP

Benign

0.017

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.70

REVEL

Benign

0.074

Sift

Pathogenic

0.0

Sift4G

Benign

0.22

Polyphen

1.0

Vest4

0.31

MVP

0.26

MPC

0.042

ClinPred

0.064

GERP RS

3.4

Varity_R

0.17

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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