17-41620565-GA-G

Position:

• chr17-41620565-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000422.3(KRT17):​c.1182-8del variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.262

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 1584045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-41620565-GA-G is described in Lovd as [Benign]. Variant chr17-41620565-GA-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT17	NM_000422.3	c.1182-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000311208.13	NP_000413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT17	ENST00000311208.13	c.1182-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000422.3	ENSP00000308452	P1
KRT17	ENST00000648859.1	c.172-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				ENSP00000497161
KRT17	ENST00000493253.5	n.1569-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2
KRT17	ENST00000649249.1	n.458-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

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

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

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0103

Gnomad4 ASJ exome AF: 0.000826

Gnomad4 EAS exome AF: 0.00126

Gnomad4 SAS exome AF: 0.00175

Gnomad4 FIN exome AF: 0.00205

Gnomad4 NFE exome AF: 0.00177

Gnomad4 OTH exome AF: 0.0116

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

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000998

Gnomad4 SAS AF: 0.000219

Gnomad4 FIN AF: 0.000558

Gnomad4 NFE AF: 0.000746

Gnomad4 OTH AF: 0.0262

Bravo AF: 0.0356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs528557416; hg19: chr17-39776817;