Variant 12-52608386-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000305748.7(KRT73):c.1433G>C(p.Gly478Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,613,040 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 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

KRT73
ENST00000305748.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049568415).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT73	NM_175068.3 linkuse as main transcript	c.1433G>C	p.Gly478Ala	missense_variant	9/9	ENST00000305748.7	NP_778238.1
KRT73	XM_047428761.1 linkuse as main transcript	c.1433G>C	p.Gly478Ala	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.1433G>C	p.Gly478Ala	missense_variant	9/9	1	NM_175068.3	ENSP00000307014	P1	Q86Y46-1
KRT73-AS1	ENST00000551089.5 linkuse as main transcript	n.102-2902C>G		intron_variant, non_coding_transcript_variant		4
KRT73	ENST00000552855.1 linkuse as main transcript	c.668G>C	p.Gly223Ala	missense_variant	6/6	3		ENSP00000449081
KRT73	ENST00000546934.1 linkuse as main transcript	n.1826G>C		non_coding_transcript_exon_variant	8/8	2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000157

AC:

AN:

249068

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

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:

0.000260

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000105

AC:

153

AN:

1460702

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

726660

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000164

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000246

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000533

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 12, 2022

The c.1433G>C (p.G478A) alteration is located in exon 9 (coding exon 9) of the KRT73 gene. This alteration results from a G to C substitution at nucleotide position 1433, causing the glycine (G) at amino acid position 478 to be replaced by an alanine (A). 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

0.082

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

0.98

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.18

Sift

Benign

0.78

T;T

Sift4G

Uncertain

0.025

D;D

Polyphen

0.15

B;.

Vest4

0.26

MVP

0.23

MPC

0.14

ClinPred

0.042

GERP RS

4.3

Varity_R

0.088

gMVP

0.18

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