17-40751196-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_181534.4(KRT25):c.800G>A(p.Arg267His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,614,118 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R267C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.014 ( 16 hom., cov: 32)

Exomes 𝑓: 0.019 ( 297 hom. )

Consequence

KRT25
NM_181534.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.90

Publications

15 publications found

Variant links:

Genes affected

KRT25 (HGNC:30839): (keratin 25) This gene encodes a member of the type I (acidic) keratin 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. The type I keratin genes are clustered in a region of chromosome 17q12-q21. [provided by RefSeq, Jul 2009]

KRT25 Gene-Disease associations (from GenCC):

wooly hair, autosomal recessive 3
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)
isolated familial wooly hair disorder
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRT25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008405983).

BP6

Variant 17-40751196-C-T is Benign according to our data. Variant chr17-40751196-C-T is described in ClinVar as [Benign]. Clinvar id is 2038746.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0144 (2188/152298) while in subpopulation NFE AF = 0.023 (1563/68012). AF 95% confidence interval is 0.022. There are 16 homozygotes in GnomAd4. There are 1039 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT25	NM_181534.4 link	c.800G>A	p.Arg267His	missense_variant	Exon 4 of 8	ENST00000312150.5	NP_853512.1	Q7Z3Z0Q6ZPD6
KRT25	XM_011524414.2 link	c.794G>A	p.Arg265His	missense_variant	Exon 5 of 9		XP_011522716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT25	ENST00000312150.5 link	c.800G>A	p.Arg267His	missense_variant	Exon 4 of 8	1	NM_181534.4	ENSP00000310573.4		Q7Z3Z0

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2188

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0230

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.0140

AC:

3525

AN:

251376

AF XY:

0.0137

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.00798

Gnomad ASJ exome

AF:

0.00585

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.0238

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0195

AC:

28473

AN:

1461820

Hom.:

297

Cov.:

AF XY:

0.0188

AC XY:

13695

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00355

AC:

119

AN:

33480

American (AMR)

AF:

0.00825

AC:

369

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00497

AC:

130

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00169

AC:

146

AN:

86254

European-Finnish (FIN)

AF:

0.0157

AC:

838

AN:

53420

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0233

AC:

25912

AN:

1111944

Other (OTH)

AF:

0.0158

AC:

953

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

1583

3165

4748

6330

7913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.0144

AC:

2188

AN:

152298

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1039

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00380

AC:

158

AN:

41570

American (AMR)

AF:

0.0168

AC:

257

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.00187

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0136

AC:

144

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0230

AC:

1563

AN:

68012

Other (OTH)

AF:

0.0147

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

109

218

326

435

544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0187

Hom.:

Bravo

AF:

0.0140

TwinsUK

AF:

0.0270

AC:

100

ALSPAC

AF:

0.0205

AC:

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.0197

AC:

169

ExAC

AF:

0.0147

AC:

1787

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0183

EpiControl

AF:

0.0192

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.83

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0084

MetaSVM

Uncertain

0.32

MutationAssessor

Uncertain

2.1

PhyloP100

2.9

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.53

Sift

Benign

0.033

Sift4G

Uncertain

0.010

Polyphen

0.94

Vest4

0.21

MPC

0.19

ClinPred

0.029

GERP RS

5.8

Varity_R

0.31

gMVP

0.89

Mutation Taster

=89/11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over