12-52317765-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002282.3(KRT83):c.666C>T(p.Cys222Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,611,946 control chromosomes in the GnomAD database, including 137,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13481 hom., cov: 31)

Exomes 𝑓: 0.41 ( 124406 hom. )

Consequence

KRT83
NM_002282.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.996

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

monilethrix
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
erythrokeratodermia variabilis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRT83 links:

ENSG00000296556 (HGNC:58282):

ENSG00000296556 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 12-52317765-G-A is Benign according to our data. Variant chr12-52317765-G-A is described in ClinVar as [Benign]. Clinvar id is 309525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.996 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT83	NM_002282.3 link	c.666C>T	p.Cys222Cys	synonymous_variant	Exon 4 of 9	ENST00000293670.3	NP_002273.3	P78385

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT83	ENST00000293670.3 link	c.666C>T	p.Cys222Cys	synonymous_variant	Exon 4 of 9	1	NM_002282.3	ENSP00000293670.3		P78385
ENSG00000296556	ENST00000740301.1 link	n.507-4937G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

63084

AN:

151830

Hom.:

13460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.593

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.352

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.396

GnomAD2 exomes

AF:

0.375

AC:

94369

AN:

251448

AF XY:

0.382

show subpopulations

Gnomad AFR exome

AF:

0.488

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.354

Gnomad NFE exome

AF:

0.416

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.409

AC:

596802

AN:

1459998

Hom.:

124406

Cov.:

AF XY:

0.409

AC XY:

297384

AN XY:

726378

show subpopulations

African (AFR)

AF:

0.490

AC:

16374

AN:

33440

American (AMR)

AF:

0.269

AC:

12039

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

9098

AN:

26116

East Asian (EAS)

AF:

0.208

AC:

8268

AN:

39694

South Asian (SAS)

AF:

0.428

AC:

36898

AN:

86220

European-Finnish (FIN)

AF:

0.355

AC:

18957

AN:

53416

Middle Eastern (MID)

AF:

0.380

AC:

2133

AN:

5618

European-Non Finnish (NFE)

AF:

0.422

AC:

468625

AN:

1110476

Other (OTH)

AF:

0.405

AC:

24410

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

20041

40083

60124

80166

100207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.416

AC:

63141

AN:

151948

Hom.:

13481

Cov.:

AF XY:

0.411

AC XY:

30486

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.486

AC:

20147

AN:

41458

American (AMR)

AF:

0.348

AC:

5316

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

1217

AN:

3462

East Asian (EAS)

AF:

0.203

AC:

1043

AN:

5144

South Asian (SAS)

AF:

0.428

AC:

2060

AN:

4810

European-Finnish (FIN)

AF:

0.343

AC:

3619

AN:

10558

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28262

AN:

67922

Other (OTH)

AF:

0.392

AC:

826

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1900

3800

5701

7601

9501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.311

Hom.:

1229

Bravo

AF:

0.418

EpiCase

AF:

0.418

EpiControl

AF:

0.428

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Monilethrix

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

BayesDel_noAF

Benign

-0.51

CADD

Benign

3.6

(source)

DANN

Benign

0.83

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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12-52317765-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over