Variant chr12-52424593-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004693.3(KRT75):c.1580G>A(p.Arg527Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,613,980 control chromosomes in the GnomAD database, including 22,905 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2126 hom., cov: 32)

Exomes 𝑓: 0.17 ( 20779 hom. )

Consequence

KRT75
NM_004693.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

KRT75 (HGNC:24431): (keratin 75) This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. This gene is expressed in the companion layer, upper germinative matrix region of the hair follicle, and medulla of the hair shaft. The encoded protein plays an essential role in hair and nail formation. Variations in this gene have been associated with the hair disorders pseudofolliculitis barbae (PFB) and loose anagen hair syndrome (LAHS). [provided by RefSeq, Oct 2008]

KRT75 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017234087).

BP6

Variant 12-52424593-C-T is Benign according to our data. Variant chr12-52424593-C-T is described in ClinVar as [Benign]. Clinvar id is 3059432.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT75	NM_004693.3 linkuse as main transcript	c.1580G>A	p.Arg527Gln	missense_variant	9/9	ENST00000252245.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT75	ENST00000252245.6 linkuse as main transcript	c.1580G>A	p.Arg527Gln	missense_variant	9/9	1	NM_004693.3	P1
	ENST00000548135.1 linkuse as main transcript	n.292-3564C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24147

AN:

152028

Hom.:

2118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.178

AC:

44689

AN:

251384

Hom.:

4261

AF XY:

0.175

AC XY:

23761

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.269

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.155

Gnomad SAS exome

AF:

0.179

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.168

GnomAD4 exome

AF:

0.166

AC:

242193

AN:

1461836

Hom.:

20779

Cov.:

AF XY:

0.166

AC XY:

120447

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0949

Gnomad4 AMR exome

AF:

0.264

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.161

GnomAD4 genome

AF:

0.159

AC:

24160

AN:

152144

Hom.:

2126

Cov.:

AF XY:

0.163

AC XY:

12158

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.165

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.154

Hom.:

3054

Bravo

AF:

0.156

TwinsUK

AF:

0.160

AC:

592

ALSPAC

AF:

0.160

AC:

615

ESP6500AA

AF:

0.112

AC:

495

ESP6500EA

AF:

0.163

AC:

1401

ExAC

AF:

0.170

AC:

20580

Asia WGS

AF:

0.192

AC:

665

AN:

3478

EpiCase

AF:

0.155

EpiControl

AF:

0.149

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KRT75-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.082

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.26

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

REVEL

Benign

0.25

Sift

Benign

0.045

Sift4G

Benign

0.38

Polyphen

1.0

Vest4

0.34

MPC

0.10

ClinPred

0.018

GERP RS

4.8

Varity_R

0.13

gMVP

0.59

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