17-41620536-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_000422.3(KRT17):c.1204C>T(p.Pro402Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,611,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

KRT17
NM_000422.3 missense, splice_region

Scores

Splicing: ADA: 0.04997

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.52

Variant links:

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]

KRT17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09039104).

BP6

Variant 17-41620536-G-A is Benign according to our data. Variant chr17-41620536-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2855681.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000138 (21/151716) while in subpopulation AFR AF= 0.000435 (18/41348). AF 95% confidence interval is 0.000281. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT17	NM_000422.3 linkuse as main transcript	c.1204C>T	p.Pro402Ser	missense_variant, splice_region_variant	7/8	ENST00000311208.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
KRT17	ENST00000311208.13 linkuse as main transcript	c.1204C>T	p.Pro402Ser	missense_variant, splice_region_variant	7/8	1	NM_000422.3	P1
KRT17	ENST00000648859.1 linkuse as main transcript	c.196C>T	p.Arg66Cys	missense_variant	2/2
KRT17	ENST00000493253.5 linkuse as main transcript	n.1591C>T		splice_region_variant, non_coding_transcript_exon_variant	6/7	2
KRT17	ENST00000649249.1 linkuse as main transcript	n.480C>T		splice_region_variant, non_coding_transcript_exon_variant	3/4

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151600

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000412

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000518

AC:

AN:

250810

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1459612

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726132

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000138

AC:

AN:

151716

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74100

show subpopulations

Gnomad4 AFR

AF:

0.000435

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.25

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.27

T;T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.55

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.090

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.43

N;N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.53

Polyphen

0.0

B;B;.

Vest4

0.53, 0.34

MVP

0.87

MPC

0.28

ClinPred

0.034

GERP RS

3.0

Varity_R

0.11

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.050

dbscSNV1_RF

Benign

0.16

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