Genetic Variant KRTCAP3:p.Gly124Asp (chr2-27443171-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173853.4(KRTCAP3):c.371G>A(p.Gly124Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

KRTCAP3
NM_173853.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

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=0.048459023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTCAP3	NM_173853.4 link	c.371G>A	p.Gly124Asp	missense_variant	Exon 4 of 7	ENST00000288873.7	NP_776252.2	Q53RY4-1
KRTCAP3	NM_001168364.2 link	c.371G>A	p.Gly124Asp	missense_variant	Exon 4 of 7		NP_001161836.1	Q53RY4-1
KRTCAP3	NM_001321325.2 link	c.371G>A	p.Gly124Asp	missense_variant	Exon 4 of 7		NP_001308254.1	Q53RY4-1
KRTCAP3	XM_047443704.1 link	c.371G>A	p.Gly124Asp	missense_variant	Exon 4 of 6		XP_047299660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTCAP3	ENST00000288873.7 link	c.371G>A	p.Gly124Asp	missense_variant	Exon 4 of 7	1	NM_173853.4	ENSP00000288873.3		Q53RY4-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152150

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:

0.000193

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251294

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000576

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.371G>A (p.G124D) 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 371, causing the glycine (G) at amino acid position 124 to be replaced by an aspartic acid (D). 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

0.23

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0078

T;T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.0051

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.68

T;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.66

N;N;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.36

N;N;N

REVEL

Benign

0.080

Sift

Benign

0.63

T;T;T

Sift4G

Benign

0.72

T;T;T

Polyphen

0.21

B;B;.

Vest4

0.17

MVP

0.35

MPC

0.68

ClinPred

0.091

GERP RS

4.9

Varity_R

0.17

gMVP

0.49

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