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GeneBe

17-41619618-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000422.3(KRT17):c.1275G>A(p.Glu425=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,612,184 control chromosomes in the GnomAD database, including 710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 54 hom., cov: 32)
Exomes 𝑓: 0.028 ( 656 hom. )

Consequence

KRT17
NM_000422.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.13
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-41619618-C-T is Benign according to our data. Variant chr17-41619618-C-T is described in ClinVar as [Benign]. Clinvar id is 1599894.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.13 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0212 (3236/152288) while in subpopulation NFE AF= 0.0305 (2071/68000). AF 95% confidence interval is 0.0294. There are 54 homozygotes in gnomad4. There are 1536 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 3237 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KRT17NM_000422.3 linkuse as main transcriptc.1275G>A p.Glu425= synonymous_variant 8/8 ENST00000311208.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KRT17ENST00000311208.13 linkuse as main transcriptc.1275G>A p.Glu425= synonymous_variant 8/81 NM_000422.3 P1
KRT17ENST00000493253.5 linkuse as main transcriptn.1662G>A non_coding_transcript_exon_variant 7/72
KRT17ENST00000649249.1 linkuse as main transcriptn.551G>A non_coding_transcript_exon_variant 4/4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0213
AC:
3237
AN:
152170
Hom.:
53
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00654
Gnomad AMI
AF:
0.0385
Gnomad AMR
AF:
0.0281
Gnomad ASJ
AF:
0.0308
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00621
Gnomad FIN
AF:
0.0202
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.0305
Gnomad OTH
AF:
0.0330
GnomAD3 exomes
AF:
0.0216
AC:
5424
AN:
251130
Hom.:
83
AF XY:
0.0214
AC XY:
2906
AN XY:
135746
show subpopulations
Gnomad AFR exome
AF:
0.00480
Gnomad AMR exome
AF:
0.0215
Gnomad ASJ exome
AF:
0.0296
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00552
Gnomad FIN exome
AF:
0.0209
Gnomad NFE exome
AF:
0.0307
Gnomad OTH exome
AF:
0.0326
GnomAD4 exome
AF:
0.0279
AC:
40796
AN:
1459896
Hom.:
656
Cov.:
32
AF XY:
0.0273
AC XY:
19833
AN XY:
726246
show subpopulations
Gnomad4 AFR exome
AF:
0.00464
Gnomad4 AMR exome
AF:
0.0225
Gnomad4 ASJ exome
AF:
0.0292
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00602
Gnomad4 FIN exome
AF:
0.0214
Gnomad4 NFE exome
AF:
0.0319
Gnomad4 OTH exome
AF:
0.0278
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0212
AC:
3236
AN:
152288
Hom.:
54
Cov.:
32
AF XY:
0.0206
AC XY:
1536
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00652
Gnomad4 AMR
AF:
0.0280
Gnomad4 ASJ
AF:
0.0308
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00621
Gnomad4 FIN
AF:
0.0202
Gnomad4 NFE
AF:
0.0305
Gnomad4 OTH
AF:
0.0327
Alfa
AF:
0.0276
Hom.:
28
Bravo
AF:
0.0214
Asia WGS
AF:
0.00289
AC:
11
AN:
3478
EpiCase
AF:
0.0320
EpiControl
AF:
0.0339

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
13
Dann
Benign
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs117941474; hg19: chr17-39775870; API