17-41567199-A-G

Position:

• chr17-41567199-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000226.4(KRT9):​c.*40+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,609,798 control chromosomes in the GnomAD database, including 261,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (23918 hom., cov: 29)
  • Exomes 𝑓: 0.56 (237099 hom.)
• Consequence: KRT9 NM_000226.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.509

Genes affected

KRT9 (HGNC:6447): (keratin 9) This gene encodes the type I keratin 9, an intermediate filament chain expressed only in the terminally differentiated epidermis of palms and soles. Mutations in this gene cause epidermolytic palmoplantar keratoderma. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-41567199-A-G is Benign according to our data. Variant chr17-41567199-A-G is described in ClinVar as [Benign]. Clinvar id is 1252974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT9	NM_000226.4	c.*40+34T>C		intron_variant		ENST00000246662.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT9	ENST00000246662.9	c.*40+34T>C		intron_variant		1	NM_000226.4	P1
KRT9	ENST00000588431.1	c.*40+34T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 83461 AN: 150506 Hom.: 23901 Cov.: 29

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.445

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.563 AC: 821047 AN: 1459192 Hom.: 237099 Cov.: 56 AF XY: 0.566 AC XY: 410858 AN XY: 725736

Gnomad4 AFR exome AF: 0.462

Gnomad4 AMR exome AF: 0.755

Gnomad4 ASJ exome AF: 0.584

Gnomad4 EAS exome AF: 0.957

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.615

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.555 AC: 83522 AN: 150606 Hom.: 23918 Cov.: 29 AF XY: 0.563 AC XY: 41378 AN XY: 73482

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.540

Alfa AF: 0.528 Hom.: 3643

Bravo AF: 0.554

Asia WGS AF: 0.804 AC: 2796 AN: 3478

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

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.76

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: rs6503636; hg19: chr17-39723451;