17-40818360-T-C

Position:

• chr17-40818360-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000421.5(KRT10):​c.*116A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,421,420 control chromosomes in the GnomAD database, including 25,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2212 hom., cov: 32)
  • Exomes 𝑓: 0.18 (22909 hom.)
• Consequence: KRT10 NM_000421.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.120

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-40818360-T-C is Benign according to our data. Variant chr17-40818360-T-C is described in ClinVar as [Benign]. Clinvar id is 1180230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT10	NM_000421.5	c.*116A>G		3_prime_UTR_variant	8/8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1	c.*16A>G		3_prime_UTR_variant	8/8		NP_001366295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576	c.*116A>G		3_prime_UTR_variant	8/8	1	NM_000421.5	ENSP00000269576.5
KRT10	ENST00000635956	c.*16A>G		3_prime_UTR_variant	8/8	2		ENSP00000490524.2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 25004 AN: 152038 Hom.: 2210 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.183 AC: 232397 AN: 1269264 Hom.: 22909 Cov.: 17 AF XY: 0.183 AC XY: 116340 AN XY: 637430

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.00102

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.164 AC: 25009 AN: 152156 Hom.: 2212 Cov.: 32 AF XY: 0.162 AC XY: 12021 AN XY: 74400

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.00327

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.166

Alfa AF: 0.182 Hom.: 991

Bravo AF: 0.158

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.3
DANN	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1132367; hg19: chr17-38974612;