Genetic Variant KRT36:p.Thr315Met (chr17-41487394-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003771.5(KRT36):c.944C>T(p.Thr315Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,612,810 control chromosomes in the GnomAD database, including 240,108 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 19674 hom., cov: 33)

Exomes 𝑓: 0.55 ( 220434 hom. )

Consequence

KRT36
NM_003771.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.646

Publications

32 publications found

Variant links:

Genes affected

KRT36 (HGNC:6454): (keratin 36) The protein encoded by this gene is a member of the keratin gene family. This type I hair keratin is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. [provided by RefSeq, Jul 2008]

KRT36 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.09239E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT36	NM_003771.5 link	c.944C>T	p.Thr315Met	missense_variant	Exon 5 of 7	ENST00000328119.11	NP_003762.1	O76013-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT36	ENST00000328119.11 link	c.944C>T	p.Thr315Met	missense_variant	Exon 5 of 7	2	NM_003771.5	ENSP00000329165.6		O76013-1
KRT36	ENST00000393986.2 link	c.794C>T	p.Thr265Met	missense_variant	Exon 6 of 8	1		ENSP00000377555.2		O76013-2

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76389

AN:

151988

Hom.:

19663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.648

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.519

GnomAD2 exomes

AF:

0.546

AC:

136215

AN:

249640

AF XY:

0.553

show subpopulations

Gnomad AFR exome

AF:

0.406

Gnomad AMR exome

AF:

0.593

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.349

Gnomad FIN exome

AF:

0.529

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.556

GnomAD4 exome

AF:

0.546

AC:

798076

AN:

1460706

Hom.:

220434

Cov.:

AF XY:

0.551

AC XY:

400237

AN XY:

726618

show subpopulations

African (AFR)

AF:

0.394

AC:

13185

AN:

33456

American (AMR)

AF:

0.581

AC:

25930

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.553

AC:

14445

AN:

26132

East Asian (EAS)

AF:

0.318

AC:

12611

AN:

39682

South Asian (SAS)

AF:

0.662

AC:

57037

AN:

86200

European-Finnish (FIN)

AF:

0.533

AC:

28366

AN:

53228

Middle Eastern (MID)

AF:

0.574

AC:

3171

AN:

5524

European-Non Finnish (NFE)

AF:

0.550

AC:

610804

AN:

1111556

Other (OTH)

AF:

0.539

AC:

32527

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

20890

41780

62669

83559

104449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17170

34340

51510

68680

85850

<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:

0.502

AC:

76428

AN:

152104

Hom.:

19674

Cov.:

AF XY:

0.501

AC XY:

37228

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.407

AC:

16868

AN:

41470

American (AMR)

AF:

0.510

AC:

7806

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.550

AC:

1908

AN:

3472

East Asian (EAS)

AF:

0.338

AC:

1746

AN:

5166

South Asian (SAS)

AF:

0.649

AC:

3133

AN:

4828

European-Finnish (FIN)

AF:

0.524

AC:

5543

AN:

10582

Middle Eastern (MID)

AF:

0.545

AC:

159

AN:

292

European-Non Finnish (NFE)

AF:

0.553

AC:

37614

AN:

67980

Other (OTH)

AF:

0.515

AC:

1084

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1996

3992

5989

7985

9981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.538

Hom.:

54834

Bravo

AF:

0.498

TwinsUK

AF:

0.550

AC:

2039

ALSPAC

AF:

0.563

AC:

2170

ESP6500AA

AF:

0.414

AC:

1824

ESP6500EA

AF:

0.547

AC:

4702

ExAC

AF:

0.547

AC:

66386

Asia WGS

AF:

0.479

AC:

1667

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;.

Eigen

Benign

-0.077

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.000091

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.7

M;.

PhyloP100

-0.65

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.82

P;.

Vest4

0.070

MPC

0.70

ClinPred

0.055

GERP RS

1.1

Varity_R

0.40

gMVP

0.39

Mutation Taster

=95/5

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over