rs35380497

Variant names:

• chr17-41583199-TG-T
• rs35380497
• NM_000526.5:c.1274+35delC

Your query was ambiguous. Multiple possible variants found:

• chr17-41583199-TG-T
• chr17-41583199-TG-TGG
• chr17-41583199-TG-TGGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000526.5(KRT14):​c.1274+35delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,554,068 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 0.000034 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: KRT14 NM_000526.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217
• Publications: 1 publications found

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]

KRT14 Gene-Disease associations (from GenCC):

• epidermolysis bullosa simplex 1A, generalized severe

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet
• Naegeli-Franceschetti-Jadassohn syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet, Genomics England PanelApp
• epidermolysis bullosa simplex

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, Orphanet
• dermatopathia pigmentosa reticularis

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
• epidermolysis bullosa simplex 1B, generalized intermediate

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• epidermolysis bullosa simplex 1C, localized

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• epidermolysis bullosa simplex 2F, with mottled pigmentation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000526.5. 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
	KRT14	NM_000526.5	MANE Select	c.1274+35delC		intron	N/A	NP_000517.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT14	ENST00000167586.7	TSL:1 MANE Select	c.1274+35delC		intron	N/A	ENSP00000167586.6	P02533
	KRT14	ENST00000441550.2	TSL:2	n.221+35delC		intron	N/A
	KRT14	ENST00000476662.1	TSL:2	n.*49delC		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0000341 AC: 5 AN: 146560 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000204

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: 0.0000301

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000113 AC: 28 AN: 247756 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000643

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000358

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000526 AC: 74 AN: 1407396 Hom.: 0 Cov.: 32 AF XY: 0.0000626 AC XY: 44 AN XY: 702600

African (AFR) AF: 0.00 AC: 0 AN: 32462

American (AMR) AF: 0.000449 AC: 20 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25748

East Asian (EAS) AF: 0.0000511 AC: 2 AN: 39174

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5192

European-Non Finnish (NFE) AF: 0.0000441 AC: 47 AN: 1064856

Other (OTH) AF: 0.0000513 AC: 3 AN: 58464

GnomAD4 genome AF: 0.0000341 AC: 5 AN: 146672 Hom.: 0 Cov.: 31 AF XY: 0.0000280 AC XY: 2 AN XY: 71528

African (AFR) AF: 0.00 AC: 0 AN: 39548

American (AMR) AF: 0.000204 AC: 3 AN: 14716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 4950

South Asian (SAS) AF: 0.00 AC: 0 AN: 4594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000301 AC: 2 AN: 66392

Other (OTH) AF: 0.00 AC: 0 AN: 2034

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.0000680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism

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: rs35380497; hg19: chr17-39739451; COSMIC: COSV51420217; COSMIC: COSV51420217;