Variant 17-41620779-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000422.3(KRT17):c.1061C>A(p.Ala354Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KRT17
NM_000422.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.634

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40800062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT17	NM_000422.3 linkuse as main transcript	c.1061C>A	p.Ala354Asp	missense_variant	6/8	ENST00000311208.13	NP_000413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KRT17	ENST00000311208.13 linkuse as main transcript	c.1061C>A	p.Ala354Asp	missense_variant	6/8	1	NM_000422.3	ENSP00000308452	P1
KRT17	ENST00000648859.1 linkuse as main transcript	c.53C>A	p.Ala18Asp	missense_variant	1/2			ENSP00000497161
KRT17	ENST00000493253.5 linkuse as main transcript	n.1448C>A		non_coding_transcript_exon_variant	5/7	2
KRT17	ENST00000649249.1 linkuse as main transcript	n.337C>A		non_coding_transcript_exon_variant	2/4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460526

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.1061C>A (p.A354D) alteration is located in exon 6 (coding exon 6) of the KRT17 gene. This alteration results from a C to A substitution at nucleotide position 1061, causing the alanine (A) at amino acid position 354 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.76

D;D;D

Eigen

Benign

0.10

Eigen_PC

Benign

-0.0085

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.64

.;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Uncertain

-0.088

MutationAssessor

Uncertain

2.4

M;M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.2

.;D;.

REVEL

Uncertain

0.64

Sift

Uncertain

0.023

.;D;.

Sift4G

Benign

0.096

.;T;D

Polyphen

0.92

P;P;.

Vest4

0.70, 0.76

MutPred

0.45

Gain of disorder (P = 0.0399);Gain of disorder (P = 0.0399);.;

MVP

0.96

MPC

0.73

ClinPred

0.97

GERP RS

3.0

Varity_R

0.55

gMVP

0.63

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over