Variant chr12-52608297-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000305748.7(KRT73):c.1522C>T(p.Arg508Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000894 in 1,613,822 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 2 hom. )

Consequence

KRT73
ENST00000305748.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.415

Variant links:

Genes affected

KRT73 (HGNC:28928): (keratin 73) 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 a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT73 links:

KRT73-AS1 (HGNC:49607): (KRT73 antisense RNA 1)

KRT73-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03374222).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT73	NM_175068.3 linkuse as main transcript	c.1522C>T	p.Arg508Cys	missense_variant	9/9	ENST00000305748.7	NP_778238.1
KRT73	XM_047428761.1 linkuse as main transcript	c.1522C>T	p.Arg508Cys	missense_variant	11/11		XP_047284717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT73	ENST00000305748.7 linkuse as main transcript	c.1522C>T	p.Arg508Cys	missense_variant	9/9	1	NM_175068.3	ENSP00000307014	P1	Q86Y46-1
KRT73-AS1	ENST00000551089.5 linkuse as main transcript	n.102-2991G>A		intron_variant, non_coding_transcript_variant		4
KRT73	ENST00000552855.1 linkuse as main transcript	c.757C>T	p.Arg253Cys	missense_variant	6/6	3		ENSP00000449081
KRT73	ENST00000546934.1 linkuse as main transcript	n.1915C>T		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000502

AC:

126

AN:

250810

Hom.:

AF XY:

0.000443

AC XY:

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000970

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000941

AC:

1376

AN:

1461596

Hom.:

Cov.:

AF XY:

0.000916

AC XY:

666

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00118

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000440

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000759

Hom.:

Bravo

AF:

0.000450

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000642

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.00130

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

May 26, 2022

The c.1522C>T (p.R508C) alteration is located in exon 9 (coding exon 9) of the KRT73 gene. This alteration results from a C to T substitution at nucleotide position 1522, causing the arginine (R) at amino acid position 508 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.98

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

N;N

REVEL

Uncertain

0.46

Sift

Benign

0.030

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.028

B;.

Vest4

0.23

MVP

0.41

MPC

0.18

ClinPred

0.019

GERP RS

3.2

Varity_R

0.076

gMVP

0.27

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