Genetic Variant KRTCAP3:p.Gly204Ala (chr2-27443528-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173853.4(KRTCAP3):c.611G>C(p.Gly204Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G204E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

KRTCAP3
NM_173853.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.211

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021116555).

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.611G>C	p.Gly204Ala	missense	Exon 5 of 7	NP_776252.2	Q53RY4-1
KRTCAP3	NM_001168364.2		c.611G>C	p.Gly204Ala	missense	Exon 5 of 7	NP_001161836.1	Q53RY4-1
KRTCAP3	NM_001321325.2		c.611G>C	p.Gly204Ala	missense	Exon 5 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.611G>C	p.Gly204Ala	missense	Exon 5 of 7	ENSP00000288873.3	Q53RY4-1
KRTCAP3	ENST00000543753.5	TSL:5	c.611G>C	p.Gly204Ala	missense	Exon 5 of 7	ENSP00000442400.1	Q53RY4-1
KRTCAP3	ENST00000872248.1		c.611G>C	p.Gly204Ala	missense	Exon 5 of 7	ENSP00000542307.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000318

AC:

AN:

251226

AF XY:

0.0000589

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000383

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111970

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.22

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0069

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.76

M_CAP

Benign

0.0061

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-0.21

PrimateAI

Benign

0.26

PROVEAN

Benign

0.61

REVEL

Benign

0.045

Sift

Benign

0.60

Sift4G

Benign

0.64

Polyphen

0.0010

Vest4

0.15

MutPred

0.21

Gain of helix (P = 0.027)

MVP

0.15

MPC

0.14

ClinPred

0.016

GERP RS

-10

PromoterAI

0.041

Neutral

(source)

Varity_R

0.045

gMVP

0.16

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over