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17-40818906-C-G

Variant summary

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

The NM_000421.5(KRT10):c.1629G>C(p.Gly543=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,110,904 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0084 ( 0 hom., cov: 23)
Exomes 𝑓: 0.0099 ( 12 hom. )
Failed GnomAD Quality Control

Consequence

KRT10
NM_000421.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.328
Variant links:
Genes affected
KRT10 (HGNC:6413): (keratin 10) This gene encodes a member of the type I (acidic) cytokeratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. Mutations in this gene are associated with epidermolytic hyperkeratosis. This gene is located within a cluster of keratin family members on chromosome 17q21. [provided by RefSeq, Jul 2008]

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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=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-40818906-C-G is Benign according to our data. Variant chr17-40818906-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1569698.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=-0.328 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00994 (11044/1110904) while in subpopulation AFR AF= 0.0256 (490/19130). AF 95% confidence interval is 0.0237. There are 12 homozygotes in gnomad4_exome. There are 5328 alleles in male gnomad4_exome subpopulation. Median coverage is 30. 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 Homozygotes in GnomAdExome at 2 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KRT10NM_000421.5 linkuse as main transcriptc.1629G>C p.Gly543= synonymous_variant 7/8 ENST00000269576.6
KRT10NM_001379366.1 linkuse as main transcriptc.1629G>C p.Gly543= synonymous_variant 7/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KRT10ENST00000269576.6 linkuse as main transcriptc.1629G>C p.Gly543= synonymous_variant 7/81 NM_000421.5 P2
KRT10ENST00000635956.2 linkuse as main transcriptc.1629G>C p.Gly543= synonymous_variant 7/82 A2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00
AC:
710
AN:
84274
Hom.:
0
Cov.:
23
FAILED QC
Gnomad AFR
AF:
0.0185
Gnomad AMI
AF:
0.00330
Gnomad AMR
AF:
0.00324
Gnomad ASJ
AF:
0.00321
Gnomad EAS
AF:
0.0347
Gnomad SAS
AF:
0.0106
Gnomad FIN
AF:
0.00480
Gnomad MID
AF:
0.00877
Gnomad NFE
AF:
0.00544
Gnomad OTH
AF:
0.0108
GnomAD3 exomes
AF:
0.00122
AC:
104
AN:
85572
Hom.:
2
AF XY:
0.00131
AC XY:
64
AN XY:
48744
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000554
Gnomad ASJ exome
AF:
0.00140
Gnomad EAS exome
AF:
0.00340
Gnomad SAS exome
AF:
0.000842
Gnomad FIN exome
AF:
0.00214
Gnomad NFE exome
AF:
0.00117
Gnomad OTH exome
AF:
0.00335
GnomAD4 exome
AF:
0.00994
AC:
11044
AN:
1110904
Hom.:
12
Cov.:
30
AF XY:
0.00978
AC XY:
5328
AN XY:
544712
show subpopulations
Gnomad4 AFR exome
AF:
0.0256
Gnomad4 AMR exome
AF:
0.00564
Gnomad4 ASJ exome
AF:
0.00825
Gnomad4 EAS exome
AF:
0.0121
Gnomad4 SAS exome
AF:
0.0139
Gnomad4 FIN exome
AF:
0.00333
Gnomad4 NFE exome
AF:
0.00960
Gnomad4 OTH exome
AF:
0.0114
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00841
AC:
709
AN:
84352
Hom.:
0
Cov.:
23
AF XY:
0.00797
AC XY:
327
AN XY:
41042
show subpopulations
Gnomad4 AFR
AF:
0.0184
Gnomad4 AMR
AF:
0.00323
Gnomad4 ASJ
AF:
0.00321
Gnomad4 EAS
AF:
0.0348
Gnomad4 SAS
AF:
0.0106
Gnomad4 FIN
AF:
0.00480
Gnomad4 NFE
AF:
0.00544
Gnomad4 OTH
AF:
0.0106

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 testingInvitaeOct 19, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
Cadd
Benign
4.3
Dann
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2

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.

Other links and lift over

dbSNP: rs370288912; hg19: chr17-38975158; COSMIC: COSV54090024; COSMIC: COSV54090024; API