rs761400509

Variant names:

• chr17-40819075-TGGCCGCCGCCGG-T
• rs761400509
• NM_000421.5:c.1448_1459delCCGGCGGCGGCC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM4 BP6

The NM_000421.5(KRT10):​c.1448_1459delCCGGCGGCGGCC​(p.Ser483_His487delinsTyr) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 1,215,240 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00061 (0 hom.)
• Consequence: KRT10 NM_000421.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.66
• Publications: 1 publications found

Genes affected

KRT10 (HGNC:6413): (keratin 10) This gene encodes a member of the type I (acidic) cytokeratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. Mutations in this gene are associated with epidermolytic hyperkeratosis. This gene is located within a cluster of keratin family members on chromosome 17q21. [provided by RefSeq, Jul 2008]

KRT10-AS1 (HGNC:28305): (KRT10 antisense RNA 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000421.5.
• BP6: Variant 17-40819075-TGGCCGCCGCCGG-T is Benign according to our data. Variant chr17-40819075-TGGCCGCCGCCGG-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3049296.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000421.5. 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
	KRT10	NM_000421.5	MANE Select	c.1448_1459delCCGGCGGCGGCC	p.Ser483_His487delinsTyr	disruptive_inframe_deletion	Exon 7 of 8	NP_000412.4
	KRT10	NM_001379366.1		c.1448_1459delCCGGCGGCGGCC	p.Ser483_His487delinsTyr	disruptive_inframe_deletion	Exon 7 of 8	NP_001366295.1	A0A1B0GVI3
	KRT10-AS1	NR_160886.1		n.-109_-98delGGCCGCCGCCGG		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT10	ENST00000269576.6	TSL:1 MANE Select	c.1448_1459delCCGGCGGCGGCC	p.Ser483_His487delinsTyr	disruptive_inframe_deletion	Exon 7 of 8	ENSP00000269576.5	P13645
	KRT10	ENST00000635956.2	TSL:2	c.1448_1459delCCGGCGGCGGCC	p.Ser483_His487delinsTyr	disruptive_inframe_deletion	Exon 7 of 8	ENSP00000490524.2	A0A1B0GVI3
	KRT10-AS1	ENST00000436612.7	TSL:2	n.6_17delGGCCGCCGCCGG		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00258 AC: 275 AN: 106732 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00644

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00205

Gnomad SAS AF: 0.00478

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000550

Gnomad OTH AF: 0.00562

GnomAD2 exomes AF: 0.000955 AC: 59 AN: 61774 AF XY: 0.000962

Gnomad AFR exome AF: 0.00706

Gnomad AMR exome AF: 0.000524

Gnomad ASJ exome AF: 0.000194

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000588

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000609 AC: 675 AN: 1108432 Hom.: 0 AF XY: 0.000627 AC XY: 343 AN XY: 546724

African (AFR) AF: 0.00653 AC: 159 AN: 24364

American (AMR) AF: 0.000770 AC: 15 AN: 19472

Ashkenazi Jewish (ASJ) AF: 0.000106 AC: 2 AN: 18956

East Asian (EAS) AF: 0.000686 AC: 15 AN: 21860

South Asian (SAS) AF: 0.00250 AC: 155 AN: 61952

European-Finnish (FIN) AF: 0.000109 AC: 3 AN: 27588

Middle Eastern (MID) AF: 0.00314 AC: 11 AN: 3498

European-Non Finnish (NFE) AF: 0.000286 AC: 253 AN: 884876

Other (OTH) AF: 0.00135 AC: 62 AN: 45866

GnomAD4 genome AF: 0.00258 AC: 276 AN: 106808 Hom.: 0 Cov.: 24 AF XY: 0.00267 AC XY: 139 AN XY: 52106

African (AFR) AF: 0.00645 AC: 207 AN: 32100

American (AMR) AF: 0.00135 AC: 15 AN: 11130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2330

East Asian (EAS) AF: 0.00206 AC: 6 AN: 2916

South Asian (SAS) AF: 0.00481 AC: 14 AN: 2910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 150

European-Non Finnish (NFE) AF: 0.000550 AC: 26 AN: 47244

Other (OTH) AF: 0.00554 AC: 8 AN: 1444

Alfa AF: 0.0000843 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	KRT10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7
Mutation Taster		=146/54	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs761400509; hg19: chr17-38975327;