Variant 17-40818903-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.14

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]

KRT10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT10	NM_000421.5 linkuse as main transcript	c.1632C>A	p.Gly544=	synonymous_variant	7/8	ENST00000269576.6	NP_000412.4
KRT10	NM_001379366.1 linkuse as main transcript	c.1632C>A	p.Gly544=	synonymous_variant	7/8		NP_001366295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT10	ENST00000269576.6 linkuse as main transcript	c.1632C>A	p.Gly544=	synonymous_variant	7/8	1	NM_000421.5	ENSP00000269576	P2
KRT10	ENST00000635956.2 linkuse as main transcript	c.1632C>A	p.Gly544=	synonymous_variant	7/8	2		ENSP00000490524	A2

Frequencies

GnomAD3 genomes

AF:

0.00560

AC:

833

AN:

148664

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00885

AC XY:

511

AN XY:

57730

show subpopulations

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.:

AF XY:

0.00605

AC XY:

3774

AN XY:

624100

show subpopulations

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.:

Cov.:

AF XY:

0.00590

AC XY:

429

AN XY:

72682

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

-0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over