Variant chr12-52233406-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005556.4(KRT7):c.110G>A(p.Ser37Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,564,380 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

KRT7
NM_005556.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.120

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:

KRT7 (HGNC:):

KRT7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015287042).

BP6

Variant 12-52233406-G-A is Benign according to our data. Variant chr12-52233406-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 790656.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT7	NM_005556.4 linkuse as main transcript	c.110G>A	p.Ser37Asn	missense_variant	1/9	ENST00000331817.6	NP_005547.3	P08729
KRT7	XM_011538325.3 linkuse as main transcript	c.110G>A	p.Ser37Asn	missense_variant	1/8		XP_011536627.1
KRT7	XM_047428827.1 linkuse as main transcript	c.110G>A	p.Ser37Asn	missense_variant	1/7		XP_047284783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT7	ENST00000331817.6 linkuse as main transcript	c.110G>A	p.Ser37Asn	missense_variant	1/9	1	NM_005556.4	ENSP00000329243.5		P08729
KRT7	ENST00000546666.1 linkuse as main transcript	n.258G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000149

AC:

AN:

174850

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

98660

show subpopulations

Gnomad AFR exome

AF:

0.00301

Gnomad AMR exome

AF:

0.000234

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000765

AC:

108

AN:

1412182

Hom.:

Cov.:

AF XY:

0.0000570

AC XY:

AN XY:

701680

show subpopulations

Gnomad4 AFR exome

AF:

0.00309

Gnomad4 AMR exome

AF:

0.000189

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:

0.00

Gnomad4 OTH exome

AF:

0.000224

GnomAD4 genome

AF:

0.000677

AC:

103

AN:

152198

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000271

Hom.:

Bravo

AF:

0.000835

ExAC

AF:

0.000193

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.089

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.015

MetaSVM

Uncertain

0.012

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.53

REVEL

Benign

0.22

Sift

Benign

0.17

Sift4G

Benign

0.19

Polyphen

0.017

Vest4

0.14

MVP

0.56

MPC

0.28

ClinPred

0.050

GERP RS

3.6

Varity_R

0.053

gMVP

0.40

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