dbSNP rs1664679383: KRTCAP3:p.Leu34Gln (chr2-27442651-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173853.4(KRTCAP3):c.101T>A(p.Leu34Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,427,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

KRTCAP3
NM_173853.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.101T>A	p.Leu34Gln	missense	Exon 2 of 7	NP_776252.2	Q53RY4-1
KRTCAP3	NM_001168364.2		c.101T>A	p.Leu34Gln	missense	Exon 2 of 7	NP_001161836.1	Q53RY4-1
KRTCAP3	NM_001321325.2		c.101T>A	p.Leu34Gln	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.101T>A	p.Leu34Gln	missense	Exon 2 of 7	ENSP00000288873.3	Q53RY4-1
KRTCAP3	ENST00000543753.5	TSL:5	c.101T>A	p.Leu34Gln	missense	Exon 2 of 7	ENSP00000442400.1	Q53RY4-1
KRTCAP3	ENST00000872248.1		c.101T>A	p.Leu34Gln	missense	Exon 2 of 7	ENSP00000542307.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1427456

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32464

American (AMR)

AF:

0.00

AC:

AN:

40010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23678

East Asian (EAS)

AF:

0.00

AC:

AN:

39342

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81320

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095286

Other (OTH)

AF:

0.00

AC:

AN:

58658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.086

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.49

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.7

PhyloP100

4.9

PrimateAI

Pathogenic

0.95

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.55

MutPred

0.49

Gain of catalytic residue at L34 (P = 0.0369)

MVP

0.73

MPC

0.61

ClinPred

1.0

GERP RS

5.0

PromoterAI

-0.067

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.81

gMVP

0.70

Mutation Taster

=41/59

disease causing

(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