17-41619622-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000422.3(KRT17):​c.1271G>A​(p.Arg424His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,612,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

KRT17
NM_000422.3 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.907
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.030026138).
BP6
Variant 17-41619622-C-T is Benign according to our data. Variant chr17-41619622-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 728538.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KRT17NM_000422.3 linkuse as main transcriptc.1271G>A p.Arg424His missense_variant 8/8 ENST00000311208.13 NP_000413.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRT17ENST00000311208.13 linkuse as main transcriptc.1271G>A p.Arg424His missense_variant 8/81 NM_000422.3 ENSP00000308452 P1
KRT17ENST00000493253.5 linkuse as main transcriptn.1658G>A non_coding_transcript_exon_variant 7/72
KRT17ENST00000649249.1 linkuse as main transcriptn.547G>A non_coding_transcript_exon_variant 4/4

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152154
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000175
AC:
44
AN:
251090
Hom.:
0
AF XY:
0.000111
AC XY:
15
AN XY:
135726
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00149
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000212
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000171
AC:
250
AN:
1459894
Hom.:
0
Cov.:
32
AF XY:
0.000160
AC XY:
116
AN XY:
726246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000898
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00111
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000174
Gnomad4 OTH exome
AF:
0.0000830
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152272
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000215
Hom.:
0
Bravo
AF:
0.000159
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000214
AC:
26
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 19, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T;T;T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.67
.;T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.030
T;T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
0.44
N;N;.
MutationTaster
Benign
1.0
N;D
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.3
.;N;.
REVEL
Uncertain
0.36
Sift
Benign
0.24
.;T;.
Sift4G
Benign
0.14
.;T;T
Polyphen
0.0030
B;B;.
Vest4
0.35, 0.38
MVP
0.82
MPC
0.34
ClinPred
0.059
T
GERP RS
3.5
Varity_R
0.075
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs148013099; hg19: chr17-39775874; COSMIC: COSV60861236; COSMIC: COSV60861236; API