Variant chr12-52692610-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_175078.3(KRT77):c.1238C>T(p.Ala413Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000712 in 1,403,618 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

KRT77
NM_175078.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78

Variant links:

Genes affected

KRT77 (HGNC:20411): (keratin 77) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes an epithelial keratin that is expressed in the skin and eccrine sweat glands. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT77 links:

ENSG00000257700 (HGNC:):

ENSG00000257700 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT77	NM_175078.3 link	c.1238C>T	p.Ala413Val	missense_variant	Exon 7 of 9	ENST00000341809.8	NP_778253.2	Q7Z794Q0IIN1
KRT77	XM_011538288.3 link	c.539C>T	p.Ala180Val	missense_variant	Exon 7 of 9		XP_011536590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KRT77	ENST00000341809.8 link	c.1238C>T	p.Ala413Val	missense_variant	Exon 7 of 9	1	NM_175078.3	ENSP00000342710.3	Q7Z794
KRT77	ENST00000553168.1 link	n.*576C>T		non_coding_transcript_exon_variant	Exon 8 of 10	1		ENSP00000448207.1	F8VS61
KRT77	ENST00000553168.1 link	n.*576C>T		3_prime_UTR_variant	Exon 8 of 10	1		ENSP00000448207.1	F8VS61
ENSG00000257700	ENST00000547533.1 link	n.6G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.12e-7

AC:

AN:

1403618

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696748

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:

9.38e-7

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

Mar 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1238C>T (p.A413V) alteration is located in exon 7 (coding exon 7) of the KRT77 gene. This alteration results from a C to T substitution at nucleotide position 1238, causing the alanine (A) at amino acid position 413 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

0.22

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.53

MetaSVM

Pathogenic

0.89

MutationAssessor

Uncertain

2.7

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.6

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.30

MutPred

0.40

Loss of phosphorylation at S411 (P = 0.2033);

MVP

0.97

MPC

0.73

ClinPred

0.99

GERP RS

4.5

Varity_R

0.71

gMVP

0.18

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