Genetic Variant KRT7:p.Ala44Gly (chr12-52233427-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005556.4(KRT7):c.131C>G(p.Ala44Gly) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRT7
NM_005556.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039885014).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005556.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT7	NM_005556.4	MANE Select	c.131C>G	p.Ala44Gly	missense	Exon 1 of 9	NP_005547.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT7	ENST00000331817.6	TSL:1 MANE Select	c.131C>G	p.Ala44Gly	missense	Exon 1 of 9	ENSP00000329243.5	P08729
KRT7	ENST00000955643.1		c.131C>G	p.Ala44Gly	missense	Exon 1 of 10	ENSP00000625702.1
KRT7	ENST00000955640.1		c.131C>G	p.Ala44Gly	missense	Exon 1 of 10	ENSP00000625699.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1405972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698452

African (AFR)

AF:

0.00

AC:

AN:

28350

American (AMR)

AF:

0.00

AC:

AN:

33416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24024

East Asian (EAS)

AF:

0.00

AC:

AN:

35210

South Asian (SAS)

AF:

0.00

AC:

AN:

79934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50022

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5248

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091854

Other (OTH)

AF:

0.00

AC:

AN:

57914

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

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

0.072

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.036

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.071

M_CAP

Benign

0.062

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.40

PhyloP100

1.8

PrimateAI

Uncertain

0.52

PROVEAN

Benign

2.3

REVEL

Benign

0.22

Sift

Benign

0.62

Sift4G

Benign

1.0

Polyphen

0.10

Vest4

0.13

MutPred

0.29

Loss of MoRF binding (P = 0.1121)

MVP

0.31

MPC

0.41

ClinPred

0.17

GERP RS

4.5

PromoterAI

0.016

Neutral

(source)

Varity_R

0.058

gMVP

0.46

Mutation Taster

=92/8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over