Variant rs1567759 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_175078.3(KRT77):c.658G>T(p.Gly220Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,613,712 control chromosomes in the GnomAD database, including 143,479 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.43 ( 14125 hom., cov: 31)

Exomes 𝑓: 0.42 ( 129354 hom. )

Consequence

KRT77
NM_175078.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.86

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3282895E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT77	NM_175078.3 linkuse as main transcript	c.658G>T	p.Gly220Cys	missense_variant	2/9	ENST00000341809.8	NP_778253.2	Q7Z794Q0IIN1
KRT77	XM_011538288.3 linkuse as main transcript	c.-42G>T		5_prime_UTR_premature_start_codon_gain_variant	2/9		XP_011536590.1
KRT77	XM_011538289.3 linkuse as main transcript	c.658G>T	p.Gly220Cys	missense_variant	2/5		XP_011536591.1
KRT77	XM_011538288.3 linkuse as main transcript	c.-42G>T		5_prime_UTR_variant	2/9		XP_011536590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT77	ENST00000341809.8 linkuse as main transcript	c.658G>T	p.Gly220Cys	missense_variant	2/9	1	NM_175078.3	ENSP00000342710.3		Q7Z794
KRT77	ENST00000553168.1 linkuse as main transcript	n.743G>T		non_coding_transcript_exon_variant	3/10	1		ENSP00000448207.1		F8VS61

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64854

AN:

151858

Hom.:

14091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.453

Gnomad AMI

AF:

0.647

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.402

GnomAD3 exomes

AF:

0.404

AC:

101643

AN:

251488

Hom.:

20969

AF XY:

0.406

AC XY:

55168

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.451

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.249

Gnomad SAS exome

AF:

0.424

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.425

Gnomad OTH exome

AF:

0.386

GnomAD4 exome

AF:

0.418

AC:

611501

AN:

1461736

Hom.:

129354

Cov.:

AF XY:

0.418

AC XY:

304297

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.431

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.426

Gnomad4 FIN exome

AF:

0.444

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.412

GnomAD4 genome

AF:

0.427

AC:

64930

AN:

151976

Hom.:

14125

Cov.:

AF XY:

0.425

AC XY:

31536

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.453

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.431

Gnomad4 EAS

AF:

0.245

Gnomad4 SAS

AF:

0.452

Gnomad4 FIN

AF:

0.446

Gnomad4 NFE

AF:

0.426

Gnomad4 OTH

AF:

0.408

Alfa

AF:

0.419

Hom.:

23987

Bravo

AF:

0.423

TwinsUK

AF:

0.445

AC:

1650

ALSPAC

AF:

0.439

AC:

1690

ESP6500AA

AF:

0.451

AC:

1988

ESP6500EA

AF:

0.422

AC:

3625

ExAC

AF:

0.408

AC:

49523

Asia WGS

AF:

0.420

AC:

1462

AN:

3478

EpiCase

AF:

0.417

EpiControl

AF:

0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.68

MetaRNN

Benign

0.00013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.0

REVEL

Benign

0.29

Sift

Benign

0.033

Sift4G

Uncertain

0.055

Polyphen

1.0

Vest4

0.067

MPC

0.74

ClinPred

0.032

GERP RS

-2.0

Varity_R

0.14

gMVP

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over