Variant 17-41567345-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000226.4(KRT9):c.1800C>T(p.Tyr600=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000895 in 1,613,626 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00092 ( 12 hom. )

Consequence

KRT9
NM_000226.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.173

Variant links:

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]

KRT9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 17-41567345-G-A is Benign according to our data. Variant chr17-41567345-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 323114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.173 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000657 (100/152100) while in subpopulation SAS AF= 0.0027 (13/4812). AF 95% confidence interval is 0.0016. There are 0 homozygotes in gnomad4. There are 48 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT9	NM_000226.4 linkuse as main transcript	c.1800C>T	p.Tyr600=	synonymous_variant	7/8	ENST00000246662.9	NP_000217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT9	ENST00000246662.9 linkuse as main transcript	c.1800C>T	p.Tyr600=	synonymous_variant	7/8	1	NM_000226.4	ENSP00000246662	P1
KRT9	ENST00000588431.1 linkuse as main transcript	c.1101C>T	p.Tyr367=	synonymous_variant	8/9	1		ENSP00000467932

Frequencies

GnomAD3 genomes

AF:

0.000658

AC:

100

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00104

AC:

256

AN:

247298

Hom.:

AF XY:

0.00128

AC XY:

171

AN XY:

133962

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00377

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.000988

GnomAD4 exome

AF:

0.000920

AC:

1345

AN:

1461526

Hom.:

Cov.:

146

AF XY:

0.000990

AC XY:

720

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00360

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000830

Gnomad4 OTH exome

AF:

0.000977

GnomAD4 genome

AF:

0.000657

AC:

100

AN:

152100

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000593

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 29, 2022

- -

Palmoplantar keratoderma, epidermolytic

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.4

DANN

Benign

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over