17-41347407-A-G

Variant names:

• chr17-41347407-A-G
• rs6503623
• NM_004138.4:c.589-185T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004138.4(KRT33A):​c.589-185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 152,280 control chromosomes in the GnomAD database, including 355 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 0.063 (355 hom., cov: 33)
• Consequence: KRT33A NM_004138.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004138.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT33A	NM_004138.4	MANE Select	c.589-185T>C		intron	N/A	NP_004129.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT33A	ENST00000007735.4	TSL:1 MANE Select	c.589-185T>C		intron	N/A	ENSP00000007735.3	O76009

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9661 AN: 152162 Hom.: 354 Cov.: 33

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.0427

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.0579

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0635 AC: 9668 AN: 152280 Hom.: 355 Cov.: 33 AF XY: 0.0624 AC XY: 4645 AN XY: 74462

African (AFR) AF: 0.0428 AC: 1779 AN: 41564

American (AMR) AF: 0.0446 AC: 682 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3472

East Asian (EAS) AF: 0.0422 AC: 219 AN: 5184

South Asian (SAS) AF: 0.0249 AC: 120 AN: 4820

European-Finnish (FIN) AF: 0.0876 AC: 929 AN: 10602

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0807 AC: 5491 AN: 68016

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0349 Hom.: 21

Bravo AF: 0.0610

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.74
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6503623; hg19: chr17-39503659;