Variant 12-52567039-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_175053.4(KRT74):c.1520G>T(p.Gly507Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,600,310 control chromosomes in the GnomAD database, including 6 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 4 hom. )

Consequence

KRT74
NM_175053.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.34

Variant links:

Genes affected

KRT74 (HGNC:28929): (keratin 74) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This protein belongs to a family of keratins that are specifically expressed in the inner root sheath of hair follicles.[provided by RefSeq, Jun 2009]

KRT74 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006197393).

BP6

Variant 12-52567039-C-A is Benign according to our data. Variant chr12-52567039-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 727421.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 211 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT74	NM_175053.4 linkuse as main transcript	c.1520G>T	p.Gly507Val	missense_variant	9/9	ENST00000305620.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KRT74	ENST00000305620.3 linkuse as main transcript	c.1520G>T	p.Gly507Val	missense_variant	9/9	1	NM_175053.4	P1
KRT74	ENST00000549343.5 linkuse as main transcript	c.1562G>T	p.Gly521Val	missense_variant	10/10	5
KRT74	ENST00000546384.1 linkuse as main transcript	n.507G>T		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00234

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00111

AC:

267

AN:

240856

Hom.:

AF XY:

0.00102

AC XY:

133

AN XY:

130172

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00132

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000284

Gnomad NFE exome

AF:

0.00191

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.00185

AC:

2674

AN:

1448106

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1268

AN XY:

718542

show subpopulations

Gnomad4 AFR exome

AF:

0.000422

Gnomad4 AMR exome

AF:

0.000959

Gnomad4 ASJ exome

AF:

0.0000393

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000283

Gnomad4 NFE exome

AF:

0.00227

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.00139

AC:

211

AN:

152204

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00234

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00139

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.000923

AC:

112

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

Cadd

Benign

0.048

Dann

Benign

0.83

DEOGEN2

Benign

0.068

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.20

Sift

Benign

0.24

T;T

Sift4G

Uncertain

0.049

D;D

Polyphen

0.0

.;B

Vest4

0.056

MVP

0.10

MPC

0.079

ClinPred

0.015

GERP RS

-9.0

Varity_R

0.13

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over