Variant 11-1608253-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001012708.2(KRTAP5-3):c.133G>A(p.Val45Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,601,146 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00012 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

KRTAP5-3
NM_001012708.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.226

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 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=0.13262561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-3	NM_001012708.2 linkuse as main transcript	c.133G>A	p.Val45Met	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.133G>A	p.Val45Met	missense_variant	1/1	6	NM_001012708.2	ENSP00000382592.1		Q6L8H2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

144036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000138

Gnomad ASJ

AF:

0.000298

Gnomad EAS

AF:

0.000213

Gnomad SAS

AF:

0.000228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000198

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000919

AC:

AN:

250302

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000112

AC:

163

AN:

1457110

Hom.:

Cov.:

AF XY:

0.0000966

AC XY:

AN XY:

724878

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.000125

AC:

AN:

144036

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

AN XY:

70028

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000138

Gnomad4 ASJ

AF:

0.000298

Gnomad4 EAS

AF:

0.000213

Gnomad4 SAS

AF:

0.000228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000198

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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 02, 2022

The c.133G>A (p.V45M) 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 133, causing the valine (V) at amino acid position 45 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

0.21

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

0.030

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.072

M_CAP

Benign

0.0037

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.5

PROVEAN

Benign

-0.56

REVEL

Benign

0.063

Sift

Uncertain

0.017

Sift4G

Uncertain

0.056

Polyphen

1.0

Vest4

0.17

MVP

0.18

MPC

0.021

ClinPred

0.14

GERP RS

2.8

Varity_R

0.054

gMVP

0.055

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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