rs16966703

Positions:

• chr17-41346146-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004138.4(KRT33A):​c.1188T>C​(p.Cys396=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KRT33A	NM_004138.4	c.1188T>C	p.Cys396=	synonymous_variant	7/7	ENST00000007735.4	NP_004129.2
KRT33A	XM_011524786.4	c.711T>C	p.Cys237=	synonymous_variant	5/5		XP_011523088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT33A	ENST00000007735.4	c.1188T>C	p.Cys396=	synonymous_variant	7/7	1	NM_004138.4	ENSP00000007735	P1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20753 AN: 151988 Hom.: 2167 Cov.: 32

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

GnomAD3 exomes AF: 0.0817 AC: 20548 AN: 251468 Hom.: 1383 AF XY: 0.0769 AC XY: 10450 AN XY: 135904

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 SAS exome AF: 0.0298

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.: 31 AF XY: 0.0809 AC XY: 58810 AN XY: 727034

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.0459

Gnomad4 ASJ exome AF: 0.0711

Gnomad4 EAS exome AF: 0.0489

Gnomad4 SAS exome AF: 0.0300

Gnomad4 FIN exome AF: 0.0858

Gnomad4 NFE exome AF: 0.0836

Gnomad4 OTH exome AF: 0.0853

GnomAD4 genome AF: 0.137 AC: 20817 AN: 152106 Hom.: 2182 Cov.: 32 AF XY: 0.133 AC XY: 9866 AN XY: 74332

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.0683

Gnomad4 ASJ AF: 0.0707

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.0872

Gnomad4 NFE AF: 0.0814

Gnomad4 OTH AF: 0.116

Alfa AF: 0.101 Hom.: 754

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
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs16966703; hg19: chr17-39502398; COSMIC: COSV50367129;