rs35335725

Positions:

• chr17-41059237-A-ATG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The 17-41059237-A-ATG variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 176,298 control chromosomes in the GnomAD database, including 3,787 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (3723 hom., cov: 30)
  • Exomes 𝑓: 0.015 (64 hom.)
• Consequence: KRTAP2-3 NM_001165252.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

Genes affected

KRTAP2-3 (HGNC:18906): (keratin associated protein 2-3) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP2-3	NM_001165252.2			downstream_gene_variant		ENST00000391418.3	NP_001158724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP2-3	ENST00000391418.3			downstream_gene_variant			NM_001165252.2	ENSP00000375237	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18078 AN: 151382 Hom.: 3709 Cov.: 30

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.00417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00174

Gnomad OTH AF: 0.0809

GnomAD4 exome AF: 0.0146 AC: 362 AN: 24798 Hom.: 64 Cov.: 0 AF XY: 0.0129 AC XY: 159 AN XY: 12332

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.0123

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.00189

Gnomad4 SAS exome AF: 0.00181

Gnomad4 FIN exome AF: 0.00115

Gnomad4 NFE exome AF: 0.000857

Gnomad4 OTH exome AF: 0.0283

GnomAD4 genome AF: 0.120 AC: 18139 AN: 151500 Hom.: 3723 Cov.: 30 AF XY: 0.116 AC XY: 8564 AN XY: 74096

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.0419

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.00376

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00174

Gnomad4 OTH AF: 0.0801

Alfa AF: 0.109 Hom.: 259

Bravo AF: 0.138

Asia WGS AF: 0.0270 AC: 92 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35335725; hg19: chr17-39215489;