chr17-40818434-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001379366.1(KRT10):c.1817C>T(p.Pro606Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,613,194 control chromosomes in the GnomAD database, including 395 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 231 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 164 hom. )

Consequence

KRT10
NM_001379366.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.48

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

annular epidermolytic ichthyosis
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P
congenital reticular ichthyosiform erythroderma
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
epidermolytic hyperkeratosis 2A, autosomal dominant
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
epidermolytic ichthyosis
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
ichthyosis, annular epidermolytic 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
epidermolytic hyperkeratosis 2B, autosomal recessive
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
autosomal recessive epidermolytic ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KRT10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023261607).

BP6

Variant 17-40818434-G-A is Benign according to our data. Variant chr17-40818434-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379366.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT10	NM_000421.5	MANE Select	c.*42C>T		3_prime_UTR	Exon 8 of 8	NP_000412.4
	KRT10	NM_001379366.1		c.1817C>T	p.Pro606Leu	missense	Exon 8 of 8	NP_001366295.1	A0A1B0GVI3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT10	ENST00000269576.6	TSL:1 MANE Select	c.*42C>T		3_prime_UTR	Exon 8 of 8	ENSP00000269576.5	P13645
	KRT10	ENST00000635956.2	TSL:2	c.1817C>T	p.Pro606Leu	missense	Exon 8 of 8	ENSP00000490524.2	A0A1B0GVI3

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4209

AN:

151990

Hom.:

231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0971

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00692

AC:

1720

AN:

248664

AF XY:

0.00476

show subpopulations

Gnomad AFR exome

AF:

0.0958

Gnomad AMR exome

AF:

0.00362

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00277

AC:

4041

AN:

1461086

Hom.:

164

Cov.:

AF XY:

0.00232

AC XY:

1685

AN XY:

726824

show subpopulations

African (AFR)

AF:

0.0987

AC:

3297

AN:

33418

American (AMR)

AF:

0.00447

AC:

200

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.000163

AC:

AN:

86140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00382

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000105

AC:

117

AN:

1111512

Other (OTH)

AF:

0.00648

AC:

391

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

165

331

496

662

827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0277

AC:

4211

AN:

152108

Hom.:

231

Cov.:

AF XY:

0.0268

AC XY:

1991

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0969

AC:

4019

AN:

41464

American (AMR)

AF:

0.00915

AC:

140

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68000

Other (OTH)

AF:

0.0152

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

184

367

551

734

918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0317

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0883

AC:

389

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00849

AC:

1031

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.083

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0023

PhyloP100

3.5

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over