rs142750223

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_005557.4(KRT16):c.539C>T(p.Ala180Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,609,484 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 19 hom. )

Consequence

KRT16
NM_005557.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: -0.566

Variant links:

Genes affected

KRT16 (HGNC:6423): (keratin 16) The protein encoded by this gene is a member of the keratin gene family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. Most of the type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains and are clustered in a region of chromosome 17q12-q21. This keratin has been coexpressed with keratin 14 in a number of epithelial tissues, including esophagus, tongue, and hair follicles. Mutations in this gene are associated with type 1 pachyonychia congenita, non-epidermolytic palmoplantar keratoderma and unilateral palmoplantar verrucous nevus. [provided by RefSeq, Jul 2008]

KRT16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008734137).

BP6

Variant 17-41611714-G-A is Benign according to our data. Variant chr17-41611714-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 587419.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00131 (200/152324) while in subpopulation SAS AF= 0.00787 (38/4830). AF 95% confidence interval is 0.00589. There are 0 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 200 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT16	NM_005557.4 linkuse as main transcript	c.539C>T	p.Ala180Val	missense_variant	2/8	ENST00000301653.9	NP_005548.2	P08779

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT16	ENST00000301653.9 linkuse as main transcript	c.539C>T	p.Ala180Val	missense_variant	2/8	1	NM_005557.4	ENSP00000301653.3		P08779
KRT16	ENST00000593067.1 linkuse as main transcript	c.-176C>T		5_prime_UTR_variant	3/7	3		ENSP00000467124.1		K7ENW6

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

201

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00241

AC:

579

AN:

240480

Hom.:

AF XY:

0.00287

AC XY:

372

AN XY:

129706

show subpopulations

Gnomad AFR exome

AF:

0.000199

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.000113

Gnomad SAS exome

AF:

0.00876

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00404

GnomAD4 exome

AF:

0.00157

AC:

2289

AN:

1457160

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

1328

AN XY:

724646

show subpopulations

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.00147

Gnomad4 ASJ exome

AF:

0.0142

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00878

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000784

Gnomad4 OTH exome

AF:

0.00298

GnomAD4 genome

AF:

0.00131

AC:

200

AN:

152324

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00787

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00201

Hom.:

Bravo

AF:

0.00163

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00175

AC:

ExAC

AF:

0.00217

AC:

264

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Pachyonychia congenita 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Aug 07, 2018

- -

Palmoplantar keratoderma, epidermolytic

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Aug 07, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Uncertain

0.51

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.38

M_CAP

Benign

0.069

MetaRNN

Benign

0.0087

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.20

PROVEAN

Benign

-2.1

REVEL

Benign

0.20

Sift

Benign

0.18

Sift4G

Benign

0.27

Polyphen

0.094

Vest4

0.20

MVP

0.37

MPC

0.32

ClinPred

0.0060

GERP RS

-7.8

Varity_R

0.068

gMVP

0.40

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