Variant 2-27443089-G-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_173853.4(KRTCAP3):c.289G>A(p.Ala97Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

KRTCAP3
NM_173853.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.731

Variant links:

Genes affected

KRTCAP3 (HGNC:28943): (keratinocyte associated protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KRTCAP3 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=0.041604787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRTCAP3	NM_173853.4 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	4/7	ENST00000288873.7
KRTCAP3	NM_001168364.2 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	4/7
KRTCAP3	NM_001321325.2 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	4/7
KRTCAP3	XM_047443704.1 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTCAP3	ENST00000288873.7 linkuse as main transcript	c.289G>A	p.Ala97Thr	missense_variant	4/7	1	NM_173853.4	P1	Q53RY4-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152098

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:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250872

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461570

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

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

Dec 07, 2022

The c.289G>A (p.A97T) alteration is located in exon 4 (coding exon 4) of the KRTCAP3 gene. This alteration results from a G to A substitution at nucleotide position 289, causing the alanine (A) at amino acid position 97 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

0.078

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.020

T;T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.63

T;.;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.042

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.51

N;N;N

REVEL

Benign

0.034

Sift

Benign

0.71

T;T;T

Sift4G

Benign

0.43

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.083

MutPred

0.26

Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);.;

MVP

0.32

MPC

0.14

ClinPred

0.099

GERP RS

4.9

Varity_R

0.053

gMVP

0.33

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