chr12-52314636-G-A

Position:

chr12-52314636-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002282.3(KRT83):c.1477C>T(p.His493Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,562,540 control chromosomes in the GnomAD database, including 357,051 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 41368 hom., cov: 33)

Exomes 𝑓: 0.67 ( 315683 hom. )

Consequence

KRT83
NM_002282.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.940

Variant links:

Genes affected

KRT83 (HGNC:6460): (keratin 83) The protein encoded by this gene is a member of the keratin gene family. As a type II hair keratin, it is a basic protein which heterodimerizes with type I keratins to form hair and nails. The type II hair keratins are clustered in a region of chromosome 12q13 and are grouped into two distinct subfamilies based on structure similarity. One subfamily, consisting of KRTHB1, KRTHB3, and KRTHB6, is highly related. The other less-related subfamily includes KRTHB2, KRTHB4, and KRTHB5. All hair keratins are expressed in the hair follicle; this hair keratin, as well as KRTHB1 and KRTHB6, is found primarily in the hair cortex. [provided by RefSeq, Jul 2008]

KRT83 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.666862E-7).

BP6

Variant 12-52314636-G-A is Benign according to our data. Variant chr12-52314636-G-A is described in ClinVar as [Benign]. Clinvar id is 309494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-52314636-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT83	NM_002282.3 linkuse as main transcript	c.1477C>T	p.His493Tyr	missense_variant	9/9	ENST00000293670.3	NP_002273.3	P78385

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT83	ENST00000293670.3 linkuse as main transcript	c.1477C>T	p.His493Tyr	missense_variant	9/9	1	NM_002282.3	ENSP00000293670.3		P78385

Frequencies

GnomAD3 genomes

AF:

0.727

AC:

110441

AN:

151978

Hom.:

41308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.922

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.613

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.650

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.655

Gnomad OTH

AF:

0.695

GnomAD3 exomes

AF:

0.653

AC:

114152

AN:

174816

Hom.:

37911

AF XY:

0.651

AC XY:

60275

AN XY:

92566

show subpopulations

Gnomad AFR exome

AF:

0.931

Gnomad AMR exome

AF:

0.566

Gnomad ASJ exome

AF:

0.620

Gnomad EAS exome

AF:

0.651

Gnomad SAS exome

AF:

0.662

Gnomad FIN exome

AF:

0.650

Gnomad NFE exome

AF:

0.648

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.667

AC:

940696

AN:

1410444

Hom.:

315683

Cov.:

AF XY:

0.666

AC XY:

464143

AN XY:

696810

show subpopulations

Gnomad4 AFR exome

AF:

0.936

Gnomad4 AMR exome

AF:

0.579

Gnomad4 ASJ exome

AF:

0.624

Gnomad4 EAS exome

AF:

0.665

Gnomad4 SAS exome

AF:

0.668

Gnomad4 FIN exome

AF:

0.646

Gnomad4 NFE exome

AF:

0.663

Gnomad4 OTH exome

AF:

0.678

GnomAD4 genome

AF:

0.727

AC:

110556

AN:

152096

Hom.:

41368

Cov.:

AF XY:

0.724

AC XY:

53857

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.922

Gnomad4 AMR

AF:

0.628

Gnomad4 ASJ

AF:

0.613

Gnomad4 EAS

AF:

0.677

Gnomad4 SAS

AF:

0.682

Gnomad4 FIN

AF:

0.650

Gnomad4 NFE

AF:

0.655

Gnomad4 OTH

AF:

0.697

Alfa

AF:

0.663

Hom.:

81779

Bravo

AF:

0.732

TwinsUK

AF:

0.662

AC:

2454

ALSPAC

AF:

0.671

AC:

2587

ESP6500AA

AF:

0.923

AC:

4032

ESP6500EA

AF:

0.660

AC:

5655

ExAC

AF:

0.593

AC:

66871

Asia WGS

AF:

0.714

AC:

2485

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Beaded hair

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.1

DANN

Benign

0.61

DEOGEN2

Benign

0.013

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00076

LIST_S2

Benign

0.31

MetaRNN

Benign

6.7e-7

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.43

PROVEAN

Benign

0.030

REVEL

Benign

0.22

Sift

Benign

0.45

Sift4G

Uncertain

0.0080

Polyphen

0.0

Vest4

0.069

MPC

0.084

ClinPred

0.0015

GERP RS

4.2

Varity_R

0.029

gMVP

0.13

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