Variant 12-52241520-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005556.4(KRT7):c.742T>C(p.Ser248Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KRT7
NM_005556.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRT7	NM_005556.4 linkuse as main transcript	c.742T>C	p.Ser248Pro	missense_variant	5/9	ENST00000331817.6
KRT7	XM_011538325.3 linkuse as main transcript	c.742T>C	p.Ser248Pro	missense_variant	5/8
KRT7	XM_047428827.1 linkuse as main transcript	c.742T>C	p.Ser248Pro	missense_variant	5/7
KRT7	XM_017019294.2 linkuse as main transcript	c.211T>C	p.Ser71Pro	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT7	ENST00000331817.6 linkuse as main transcript	c.742T>C	p.Ser248Pro	missense_variant	5/9	1	NM_005556.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727158

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 01, 2022

The c.742T>C (p.S248P) alteration is located in exon 5 (coding exon 5) of the KRT7 gene. This alteration results from a T to C substitution at nucleotide position 742, causing the serine (S) at amino acid position 248 to be replaced by a proline (P). 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

Pathogenic

0.66

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

D;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.33

T;T

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Uncertain

0.65

MutationAssessor

Pathogenic

3.6

H;.

MutationTaster

Benign

0.99

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-4.3

D;.

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.022

D;.

Polyphen

1.0

D;.

Vest4

0.59

MutPred

0.63

Loss of phosphorylation at S248 (P = 0.0501);.;

MVP

0.59

MPC

1.1

ClinPred

1.0

GERP RS

3.7

Varity_R

0.84

gMVP

0.62

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over