17-41620565-GAA-GA

Variant names:

• chr17-41620565-GA-G
• rs528557416
• NM_000422.3:c.1182-8delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000422.3(KRT17):​c.1182-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 145,376 control chromosomes in the GnomAD database, including 244 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (244 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (143 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRT17 NM_000422.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.262
• Publications: 0 publications found

Genes affected

KRT17 (HGNC:6427): (keratin 17) This gene encodes the type I intermediate filament chain keratin 17, expressed in nail bed, hair follicle, sebaceous glands, and other epidermal appendages. Mutations in this gene lead to Jackson-Lawler type pachyonychia congenita and steatocystoma multiplex. [provided by RefSeq, Aug 2008]

KRT17 Gene-Disease associations (from GenCC):

• sebocystomatosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• pachyonychia congenita 2

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• pachyonychia congenita

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289252 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-41620565-GA-G is Benign according to our data. Variant chr17-41620565-GA-G is described in ClinVar as Benign. ClinVar VariationId is 1584045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000422.3. 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
	KRT17	NM_000422.3	MANE Select	c.1182-8delT		splice_region intron	N/A	NP_000413.1	Q04695

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT17	ENST00000311208.13	TSL:1 MANE Select	c.1182-8delT		splice_region intron	N/A	ENSP00000308452.8	Q04695
	KRT17	ENST00000862596.1		c.1179-8delT		splice_region intron	N/A	ENSP00000532655.1
	KRT17	ENST00000648859.1		c.171-8delT		splice_region intron	N/A	ENSP00000497161.1	A0A3B3IS58

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4616 AN: 145298 Hom.: 244 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000996

Gnomad SAS AF: 0.000437

Gnomad FIN AF: 0.000558

Gnomad MID AF: 0.0200

Gnomad NFE AF: 0.000746

Gnomad OTH AF: 0.0264

GnomAD2 exomes AF: 0.0224 AC: 2160 AN: 96496 AF XY: 0.0180

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.0159

Gnomad ASJ exome AF: 0.00356

Gnomad EAS exome AF: 0.00513

Gnomad FIN exome AF: 0.00225

Gnomad NFE exome AF: 0.00579

Gnomad OTH exome AF: 0.0141

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00568 AC: 6407 AN: 1128412 Hom.: 143 Cov.: 36 AF XY: 0.00498 AC XY: 2804 AN XY: 563446

African (AFR) AF: 0.137 AC: 3706 AN: 27038

American (AMR) AF: 0.0103 AC: 355 AN: 34626

Ashkenazi Jewish (ASJ) AF: 0.000826 AC: 17 AN: 20578

East Asian (EAS) AF: 0.00126 AC: 38 AN: 30214

South Asian (SAS) AF: 0.00175 AC: 122 AN: 69530

European-Finnish (FIN) AF: 0.00205 AC: 82 AN: 39922

Middle Eastern (MID) AF: 0.0107 AC: 34 AN: 3166

European-Non Finnish (NFE) AF: 0.00177 AC: 1513 AN: 856800

Other (OTH) AF: 0.0116 AC: 540 AN: 46538

GnomAD4 genome AF: 0.0319 AC: 4632 AN: 145376 Hom.: 244 Cov.: 31 AF XY: 0.0311 AC XY: 2192 AN XY: 70504

African (AFR) AF: 0.109 AC: 4360 AN: 39920

American (AMR) AF: 0.0105 AC: 154 AN: 14674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.000998 AC: 5 AN: 5008

South Asian (SAS) AF: 0.000219 AC: 1 AN: 4564

European-Finnish (FIN) AF: 0.000558 AC: 5 AN: 8958

Middle Eastern (MID) AF: 0.0219 AC: 6 AN: 274

European-Non Finnish (NFE) AF: 0.000746 AC: 49 AN: 65702

Other (OTH) AF: 0.0262 AC: 52 AN: 1986

Alfa AF: 0.00623 Hom.: 2

Bravo AF: 0.0356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.26
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: rs528557416; hg19: chr17-39776817; COSMIC: COSV60860442; COSMIC: COSV60860442;