Variant chr1-155169544-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173852.4(KRTCAP2):c.307G>T(p.Val103Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

KRTCAP2
NM_173852.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.909

Variant links:

Genes affected

KRTCAP2 (HGNC:28942): (keratinocyte associated protein 2) Enables enzyme activator activity. Involved in protein N-linked glycosylation via arginine. Is active in oligosaccharyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

KRTCAP2 links:

ENSG00000273088 (HGNC:):

ENSG00000273088 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10301408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTCAP2	NM_173852.4 linkuse as main transcript	c.307G>T	p.Val103Phe	missense_variant	5/5	ENST00000295682.6	NP_776251.2	Q8N6L1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTCAP2	ENST00000295682.6 linkuse as main transcript	c.307G>T	p.Val103Phe	missense_variant	5/5	1	NM_173852.4	ENSP00000295682.5		Q8N6L1-1
ENSG00000273088	ENST00000473363.3 linkuse as main transcript	c.618G>T	p.Trp206Cys	missense_variant	5/5	5		ENSP00000477381.3		V9GZ38

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000111

AC:

AN:

251150

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000123

AC:

180

AN:

1461748

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000140

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000131

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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

Feb 28, 2024

The c.385G>T (p.V129F) alteration is located in exon 5 (coding exon 5) of the KRTCAP2 gene. This alteration results from a G to T substitution at nucleotide position 385, causing the valine (V) at amino acid position 129 to be replaced by a phenylalanine (F). 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

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0051

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.15

Sift

Benign

0.21

Sift4G

Benign

0.085

Vest4

0.31

MVP

0.45

MPC

0.35

ClinPred

0.064

GERP RS

3.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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