Variant 12-52691383-C-T 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.1519G>A(p.Gly507Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000468 in 1,602,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

KRT77
NM_175078.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00900

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:

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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=0.12970254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT77	NM_175078.3 linkuse as main transcript	c.1519G>A	p.Gly507Ser	missense_variant	9/9	ENST00000341809.8
KRT77	XM_011538288.3 linkuse as main transcript	c.820G>A	p.Gly274Ser	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT77	ENST00000341809.8 linkuse as main transcript	c.1519G>A	p.Gly507Ser	missense_variant	9/9	1	NM_175078.3	P1
KRT77	ENST00000553168.1 linkuse as main transcript	c.*857G>A		3_prime_UTR_variant, NMD_transcript_variant	10/10	1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000654

AC:

AN:

229358

Hom.:

AF XY:

0.0000633

AC XY:

AN XY:

126380

show subpopulations

Gnomad AFR exome

AF:

0.000213

Gnomad AMR exome

AF:

0.000208

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:

0.0000388

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.0000435

AC:

AN:

1449902

Hom.:

Cov.:

AF XY:

0.0000485

AC XY:

AN XY:

721228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000181

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:

0.0000451

Gnomad4 OTH exome

AF:

0.0000667

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000106

ExAC

AF:

0.0000502

AC:

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

Jul 27, 2022

The c.1519G>A (p.G507S) alteration is located in exon 9 (coding exon 9) of the KRT77 gene. This alteration results from a G to A substitution at nucleotide position 1519, causing the glycine (G) at amino acid position 507 to be replaced by a serine (S). 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

0.089

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.13

Cadd

Benign

6.5

Dann

Benign

0.86

DEOGEN2

Benign

0.0041

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.17

M_CAP

Benign

0.026

MetaRNN

Benign

0.13

MetaSVM

Uncertain

0.021

MutationAssessor

Benign

-0.89

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.2

REVEL

Benign

0.26

Sift

Benign

0.43

Sift4G

Benign

0.25

Polyphen

1.0

Vest4

0.21

MutPred

0.21

Gain of phosphorylation at G507 (P = 0.0056);

MVP

0.77

MPC

0.19

ClinPred

0.069

GERP RS

3.6

Varity_R

0.098

gMVP

0.54

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