Variant 12-52241620-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005556.4(KRT7):c.842C>T(p.Ala281Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000615 in 1,610,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

KRT7
NM_005556.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

KRT7 (HGNC:6445): (keratin 7) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

KRT7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33789206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRT7	NM_005556.4 linkuse as main transcript	c.842C>T	p.Ala281Val	missense_variant	5/9	ENST00000331817.6	NP_005547.3
KRT7	XM_011538325.3 linkuse as main transcript	c.842C>T	p.Ala281Val	missense_variant	5/8		XP_011536627.1
KRT7	XM_047428827.1 linkuse as main transcript	c.842C>T	p.Ala281Val	missense_variant	5/7		XP_047284783.1
KRT7	XM_017019294.2 linkuse as main transcript	c.311C>T	p.Ala104Val	missense_variant	3/7		XP_016874783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT7	ENST00000331817.6 linkuse as main transcript	c.842C>T	p.Ala281Val	missense_variant	5/9	1	NM_005556.4	ENSP00000329243	P1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000243

AC:

AN:

247204

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133564

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000537

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000638

AC:

AN:

1458188

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

725330

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000829

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

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

Dec 15, 2022

The c.842C>T (p.A281V) alteration is located in exon 5 (coding exon 5) of the KRT7 gene. This alteration results from a C to T substitution at nucleotide position 842, causing the alanine (A) at amino acid position 281 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.57

D;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.25

T;T

M_CAP

Benign

0.083

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.46

MutationAssessor

Pathogenic

2.9

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.8

D;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.012

D;.

Polyphen

0.66

P;.

Vest4

0.27

MutPred

0.47

Loss of disorder (P = 0.0882);.;

MVP

0.56

MPC

0.70

ClinPred

0.49

GERP RS

1.9

Varity_R

0.26

gMVP

0.61

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

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