Variant 12-52823211-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_175834.3(KRT79):c.1172C>T(p.Ala391Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,614,000 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 1 hom. )

Consequence

KRT79
NM_175834.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0880

Variant links:

Genes affected

KRT79 (HGNC:28930): (keratin 79) 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 skeletal muscle, skin and scalp. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT79 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04393378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT79	NM_175834.3 link	c.1172C>T	p.Ala391Val	missense_variant	7/9	ENST00000330553.6	NP_787028.1	Q5XKE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT79	ENST00000330553.6 link	c.1172C>T	p.Ala391Val	missense_variant	7/9	1	NM_175834.3	ENSP00000328358.5		Q5XKE5
KRT79	ENST00000546453.1 link	n.644C>T		non_coding_transcript_exon_variant	5/7	1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000717

AC:

AN:

250956

Hom.:

AF XY:

0.0000811

AC XY:

AN XY:

135626

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:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000527

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000533

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Feb 05, 2024

The c.1172C>T (p.A391V) alteration is located in exon 7 (coding exon 7) of the KRT79 gene. This alteration results from a C to T substitution at nucleotide position 1172, causing the alanine (A) at amino acid position 391 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

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.4

DANN

Benign

0.93

DEOGEN2

Benign

0.41

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.52

M_CAP

Benign

0.021

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.24

Sift

Uncertain

0.011

Sift4G

Uncertain

0.015

Polyphen

0.10

Vest4

0.075

MutPred

0.53

Gain of catalytic residue at A391 (P = 0.0953);

MVP

0.23

MPC

0.10

ClinPred

0.20

GERP RS

-4.6

Varity_R

0.19

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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