Genetic Variant NM_173853.4:c.61G>A (chr2-27442611-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173853.4(KRTCAP3):c.61G>A(p.Val21Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V21A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRTCAP3
NM_173853.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.167

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20959553).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173853.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTCAP3	NM_173853.4	MANE Select	c.61G>A	p.Val21Met	missense	Exon 2 of 7	NP_776252.2	Q53RY4-1
KRTCAP3	NM_001168364.2		c.61G>A	p.Val21Met	missense	Exon 2 of 7	NP_001161836.1	Q53RY4-1
KRTCAP3	NM_001321325.2		c.61G>A	p.Val21Met	missense	Exon 2 of 7	NP_001308254.1	Q53RY4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRTCAP3	ENST00000288873.7	TSL:1 MANE Select	c.61G>A	p.Val21Met	missense	Exon 2 of 7	ENSP00000288873.3	Q53RY4-1
KRTCAP3	ENST00000543753.5	TSL:5	c.61G>A	p.Val21Met	missense	Exon 2 of 7	ENSP00000442400.1	Q53RY4-1
KRTCAP3	ENST00000872248.1		c.61G>A	p.Val21Met	missense	Exon 2 of 7	ENSP00000542307.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1411752

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697540

African (AFR)

AF:

0.00

AC:

AN:

32186

American (AMR)

AF:

0.00

AC:

AN:

37680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22646

East Asian (EAS)

AF:

0.00

AC:

AN:

39052

South Asian (SAS)

AF:

0.00

AC:

AN:

78120

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5538

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087898

Other (OTH)

AF:

0.00

AC:

AN:

58102

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.079

Eigen_PC

Benign

-0.083

FATHMM_MKL

Benign

0.18

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.090

PhyloP100

0.17

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.10

REVEL

Benign

0.065

Sift

Benign

0.16

Sift4G

Benign

0.44

Polyphen

0.90

Vest4

0.33

MutPred

0.24

Gain of catalytic residue at V21 (P = 0.0342)

MVP

0.21

MPC

0.53

ClinPred

0.38

GERP RS

4.1

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.058

gMVP

0.42

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over