Variant 12-52618518-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_175068.3(KRT73):c.7C>G(p.Arg3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,597,498 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

KRT73
NM_175068.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.169

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT73	NM_175068.3 linkuse as main transcript	c.7C>G	p.Arg3Gly	missense_variant	1/9	ENST00000305748.7
KRT73	XM_047428761.1 linkuse as main transcript	c.7C>G	p.Arg3Gly	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT73	ENST00000305748.7 linkuse as main transcript	c.7C>G	p.Arg3Gly	missense_variant	1/9	1	NM_175068.3	P1	Q86Y46-1
KRT73	ENST00000546934.1 linkuse as main transcript	n.32C>G		non_coding_transcript_exon_variant	1/8	2

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000367

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000131

AC:

AN:

237038

Hom.:

AF XY:

0.000117

AC XY:

AN XY:

128370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000476

Gnomad NFE exome

AF:

0.000272

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.000261

AC:

377

AN:

1445330

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

182

AN XY:

717128

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000378

Gnomad4 NFE exome

AF:

0.000333

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.000204

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000484

Hom.:

Bravo

AF:

0.000181

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.12

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.35

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.84

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.57

MetaSVM

Pathogenic

0.80

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

0.61

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.45

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.98

Vest4

0.58

MVP

0.50

MPC

0.66

ClinPred

0.68

GERP RS

4.5

Varity_R

0.63

gMVP

0.47

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