17-41620565-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000422.3(KRT17):c.1182-8_1182-7insT 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 0.0147 in 145,326 control chromosomes in the GnomAD database, including 28 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (28 hom., cov: 31)
  • Exomes 𝑓: 0.085 (45 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-G-GA is Benign according to our data. Variant chr17-41620565-G-GA is described in ClinVar as [Benign]. Clinvar id is 1528628.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0147 (2140/145326) while in subpopulation NFE AF= 0.0195 (1281/65662). AF 95% confidence interval is 0.0186. There are 28 homozygotes in gnomad4. There are 961 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 2139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT17	NM_000422.3	c.1182-8_1182-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000311208.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT17	ENST00000311208.13	c.1182-8_1182-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000422.3	P1
KRT17	ENST00000648859.1	c.172-8_172-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
KRT17	ENST00000493253.5	n.1569-8_1569-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2
KRT17	ENST00000649249.1	n.458-8_458-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2139 AN: 145248 Hom.: 28 Cov.: 31

Gnomad AFR AF: 0.00618

Gnomad AMI AF: 0.0391

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.00612

Gnomad FIN AF: 0.00559

Gnomad MID AF: 0.0367

Gnomad NFE AF: 0.0195

Gnomad OTH AF: 0.0218

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.0852 AC: 62484 AN: 732962 Hom.: 45 Cov.: 36 AF XY: 0.0839 AC XY: 30025 AN XY: 357924

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.0633

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.0366

Gnomad4 SAS exome AF: 0.0540

Gnomad4 FIN exome AF: 0.0349

Gnomad4 NFE exome AF: 0.0918

Gnomad4 OTH exome AF: 0.0861

GnomAD4 genome AF: 0.0147 AC: 2140 AN: 145326 Hom.: 28 Cov.: 31 AF XY: 0.0136 AC XY: 961 AN XY: 70470

Gnomad4 AFR AF: 0.00616

Gnomad4 AMR AF: 0.0176

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.00120

Gnomad4 SAS AF: 0.00657

Gnomad4 FIN AF: 0.00559

Gnomad4 NFE AF: 0.0195

Gnomad4 OTH AF: 0.0217

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

Invitae

Jan 20, 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;