dbSNP rs16966703: KRT33A:p.Cys396Cys (chr17-41346146-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004138.4(KRT33A):c.1188T>C(p.Cys396Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 1,613,572 control chromosomes in the GnomAD database, including 8,565 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 2182 hom., cov: 32)

Exomes 𝑓: 0.083 ( 6383 hom. )

Consequence

KRT33A
NM_004138.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.686

Publications

18 publications found

Variant links:

Genes affected

KRT33A (HGNC:6450): (keratin 33A) This gene encodes a member of the keratin gene family. This gene is one of multiple type I hair keratin genes that are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. As a type I hair keratin, the encoded protein is an acidic protein which heterodimerizes with type II keratins to form hair and nails. There are two isoforms of this protein, encoded by two separate genes, keratin 33A and keratin 33B. [provided by RefSeq, May 2012]

KRT33A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP7

Synonymous conserved (PhyloP=-0.686 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT33A	NM_004138.4 link	c.1188T>C	p.Cys396Cys	synonymous_variant	Exon 7 of 7	ENST00000007735.4	NP_004129.2	O76009
KRT33A	XM_011524786.4 link	c.711T>C	p.Cys237Cys	synonymous_variant	Exon 5 of 5		XP_011523088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT33A	ENST00000007735.4 link	c.1188T>C	p.Cys396Cys	synonymous_variant	Exon 7 of 7	1	NM_004138.4	ENSP00000007735.3		O76009

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20753

AN:

151988

Hom.:

2167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.0684

Gnomad ASJ

AF:

0.0707

Gnomad EAS

AF:

0.0430

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.0872

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0814

Gnomad OTH

AF:

0.115

GnomAD2 exomes

AF:

0.0817

AC:

20548

AN:

251468

AF XY:

0.0769

show subpopulations

Gnomad AFR exome

AF:

0.302

Gnomad AMR exome

AF:

0.0433

Gnomad ASJ exome

AF:

0.0687

Gnomad EAS exome

AF:

0.0445

Gnomad FIN exome

AF:

0.0831

Gnomad NFE exome

AF:

0.0836

Gnomad OTH exome

AF:

0.0682

GnomAD4 exome

AF:

0.0833

AC:

121685

AN:

1461466

Hom.:

6383

Cov.:

AF XY:

0.0809

AC XY:

58810

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.307

AC:

10266

AN:

33466

American (AMR)

AF:

0.0459

AC:

2051

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0711

AC:

1858

AN:

26130

East Asian (EAS)

AF:

0.0489

AC:

1940

AN:

39698

South Asian (SAS)

AF:

0.0300

AC:

2589

AN:

86254

European-Finnish (FIN)

AF:

0.0858

AC:

4583

AN:

53418

Middle Eastern (MID)

AF:

0.0612

AC:

353

AN:

5768

European-Non Finnish (NFE)

AF:

0.0836

AC:

92892

AN:

1111622

Other (OTH)

AF:

0.0853

AC:

5153

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

5554

11107

16661

22214

27768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3498

6996

10494

13992

17490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.137

AC:

20817

AN:

152106

Hom.:

2182

Cov.:

AF XY:

0.133

AC XY:

9866

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.299

AC:

12397

AN:

41436

American (AMR)

AF:

0.0683

AC:

1044

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0707

AC:

245

AN:

3466

East Asian (EAS)

AF:

0.0425

AC:

220

AN:

5172

South Asian (SAS)

AF:

0.0253

AC:

122

AN:

4822

European-Finnish (FIN)

AF:

0.0872

AC:

924

AN:

10592

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0814

AC:

5537

AN:

68012

Other (OTH)

AF:

0.116

AC:

246

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

845

1691

2536

3382

4227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.104

Hom.:

1065

Bravo

AF:

0.145

Asia WGS

AF:

0.0640

AC:

223

AN:

3478

EpiCase

AF:

0.0822

EpiControl

AF:

0.0820

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.11

(source)

DANN

Benign

0.42

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over