17-41583199-TG-TGGG

Variant names:

• chr17-41583199-T-TGG
• rs35380497
• NM_000526.5:c.1274+34_1274+35dupCC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000526.5(KRT14):​c.1274+34_1274+35dupCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000654 in 1,407,360 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000065 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRT14 NM_000526.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217

Genes affected

KRT14 (HGNC:6416): (keratin 14) This gene encodes a member of the keratin family, the most diverse group of intermediate filaments. This gene product, a type I keratin, is usually found as a heterotetramer with two keratin 5 molecules, a type II keratin. Together they form the cytoskeleton of epithelial cells. Mutations in the genes for these keratins are associated with epidermolysis bullosa simplex. At least one pseudogene has been identified at 17p12-p11. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT14	NM_000526.5	c.1274+34_1274+35dupCC		intron_variant	Intron 6 of 7	ENST00000167586.7	NP_000517.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT14	ENST00000167586.7	c.1274+35_1274+36insCC		intron_variant	Intron 6 of 7	1	NM_000526.5	ENSP00000167586.6
KRT14	ENST00000441550.2	n.221+35_221+36insCC		intron_variant	Intron 1 of 1	2
KRT14	ENST00000476662.1	n.*49_*50insCC		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 93 AN: 146552 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000272

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000497

GnomAD3 exomes AF: 0.0000888 AC: 22 AN: 247756 Hom.: 0 AF XY: 0.0000743 AC XY: 10 AN XY: 134560

Gnomad AFR exome AF: 0.00134

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000654 AC: 92 AN: 1407360 Hom.: 0 Cov.: 32 AF XY: 0.0000541 AC XY: 38 AN XY: 702588

Gnomad4 AFR exome AF: 0.00231

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.39e-7

Gnomad4 OTH exome AF: 0.000171

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000634 AC: 93 AN: 146664 Hom.: 0 Cov.: 31 AF XY: 0.000685 AC XY: 49 AN XY: 71526

Gnomad4 AFR AF: 0.00223

Gnomad4 AMR AF: 0.000272

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000492

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: rs35380497; hg19: chr17-39739451;