17-40818903-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000421.5(KRT10):c.1632C>A(p.Gly544=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,412,036 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (112 hom.)
• Consequence: KRT10 NM_000421.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.14

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-40818903-G-T is Benign according to our data. Variant chr17-40818903-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1335270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.14 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT10	NM_000421.5	c.1632C>A	p.Gly544=	synonymous_variant	7/8	ENST00000269576.6
KRT10	NM_001379366.1	c.1632C>A	p.Gly544=	synonymous_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT10	ENST00000269576.6	c.1632C>A	p.Gly544=	synonymous_variant	7/8	1	NM_000421.5	P2
KRT10	ENST00000635956.2	c.1632C>A	p.Gly544=	synonymous_variant	7/8	2		A2

Frequencies

GnomAD3 genomes AF: 0.00560 AC: 833 AN: 148664 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000867

Gnomad AMI AF: 0.00112

Gnomad AMR AF: 0.000932

Gnomad ASJ AF: 0.0105

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00194

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00769

Gnomad OTH AF: 0.00147

GnomAD3 exomes AF: 0.00883 AC: 891 AN: 100864 Hom.: 35 AF XY: 0.00885 AC XY: 511 AN XY: 57730

Gnomad AFR exome AF: 0.00527

Gnomad AMR exome AF: 0.000447

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00276

Gnomad FIN exome AF: 0.0291

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.00624

GnomAD4 exome AF: 0.00599 AC: 7569 AN: 1263266 Hom.: 112 Cov.: 31 AF XY: 0.00605 AC XY: 3774 AN XY: 624100

Gnomad4 AFR exome AF: 0.000614

Gnomad4 AMR exome AF: 0.000634

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00302

Gnomad4 FIN exome AF: 0.0257

Gnomad4 NFE exome AF: 0.00604

Gnomad4 OTH exome AF: 0.00402

GnomAD4 genome AF: 0.00559 AC: 832 AN: 148770 Hom.: 11 Cov.: 32 AF XY: 0.00590 AC XY: 429 AN XY: 72682

Gnomad4 AFR AF: 0.000864

Gnomad4 AMR AF: 0.000931

Gnomad4 ASJ AF: 0.0105

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00194

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.00768

Gnomad4 OTH AF: 0.00145

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	KRT10: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 24, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	3.0
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

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: rs368733857; hg19: chr17-38975155;