Variant 12-52697701-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_175078.3(KRT77):c.739G>C(p.Val247Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 28)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KRT77
NM_175078.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26116472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KRT77	NM_175078.3 linkuse as main transcript	c.739G>C	p.Val247Leu	missense_variant	2/9	ENST00000341809.8
KRT77	XM_011538288.3 linkuse as main transcript	c.40G>C	p.Val14Leu	missense_variant	2/9
KRT77	XM_011538289.3 linkuse as main transcript	c.739G>C	p.Val247Leu	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT77	ENST00000341809.8 linkuse as main transcript	c.739G>C	p.Val247Leu	missense_variant	2/9	1	NM_175078.3	P1
KRT77	ENST00000553168.1 linkuse as main transcript	c.*77G>C		3_prime_UTR_variant, NMD_transcript_variant	3/10	1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726844

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Nov 09, 2023

The c.739G>C (p.V247L) alteration is located in exon 2 (coding exon 2) of the KRT77 gene. This alteration results from a G to C substitution at nucleotide position 739, causing the valine (V) at amino acid position 247 to be replaced by a leucine (L). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.84

M_CAP

Benign

0.037

MetaRNN

Benign

0.26

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.85

N;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.27

Sift

Benign

0.055

Sift4G

Benign

0.18

Polyphen

0.61

Vest4

0.18

MutPred

0.53

Loss of ubiquitination at K251 (P = 0.1612);

MVP

0.88

MPC

0.25

ClinPred

0.64

GERP RS

1.4

Varity_R

0.35

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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