dbSNP rs3782489: KRT77:p.Thr367Met (chr12-52692861-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_175078.3(KRT77):c.1100C>T(p.Thr367Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,603,032 control chromosomes in the GnomAD database, including 137,812 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 13099 hom., cov: 29)

Exomes 𝑓: 0.37 ( 124713 hom. )

Consequence

KRT77
NM_175078.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19

Publications

32 publications found

Variant links:

Genes affected

KRT77 (HGNC:20411): (keratin 77) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes an epithelial keratin that is expressed in the skin and eccrine sweat glands. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT77 links:

ENSG00000257700 (HGNC:):

ENSG00000257700 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=0.005103886).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT77	NM_175078.3 link	c.1100C>T	p.Thr367Met	missense_variant	Exon 6 of 9	ENST00000341809.8	NP_778253.2	Q7Z794Q0IIN1
KRT77	XM_011538288.3 link	c.401C>T	p.Thr134Met	missense_variant	Exon 6 of 9		XP_011536590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT77	ENST00000341809.8 link	c.1100C>T	p.Thr367Met	missense_variant	Exon 6 of 9	1	NM_175078.3	ENSP00000342710.3		Q7Z794

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

57954

AN:

149668

Hom.:

13068

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.592

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.352

GnomAD2 exomes

AF:

0.367

AC:

91635

AN:

249572

AF XY:

0.368

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.331

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.240

Gnomad FIN exome

AF:

0.413

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.373

AC:

542447

AN:

1453250

Hom.:

124713

Cov.:

AF XY:

0.374

AC XY:

270144

AN XY:

723008

show subpopulations

African (AFR)

AF:

0.426

AC:

14240

AN:

33466

American (AMR)

AF:

0.336

AC:

15013

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

10297

AN:

26024

East Asian (EAS)

AF:

0.218

AC:

8650

AN:

39700

South Asian (SAS)

AF:

0.403

AC:

34708

AN:

86048

European-Finnish (FIN)

AF:

0.413

AC:

21967

AN:

53220

Middle Eastern (MID)

AF:

0.303

AC:

1741

AN:

5746

European-Non Finnish (NFE)

AF:

0.375

AC:

413663

AN:

1104306

Other (OTH)

AF:

0.369

AC:

22168

AN:

60120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

16600

33200

49801

66401

83001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12356

24712

37068

49424

61780

<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:

0.387

AC:

58020

AN:

149782

Hom.:

13099

Cov.:

AF XY:

0.387

AC XY:

28349

AN XY:

73198

show subpopulations

African (AFR)

AF:

0.425

AC:

17484

AN:

41166

American (AMR)

AF:

0.356

AC:

5350

AN:

15038

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1335

AN:

3432

East Asian (EAS)

AF:

0.239

AC:

1228

AN:

5130

South Asian (SAS)

AF:

0.431

AC:

2032

AN:

4718

European-Finnish (FIN)

AF:

0.418

AC:

4336

AN:

10366

Middle Eastern (MID)

AF:

0.331

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.373

AC:

24906

AN:

66712

Other (OTH)

AF:

0.357

AC:

735

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1614

3229

4843

6458

8072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.379

Hom.:

22680

ESP6500AA

AF:

0.420

AC:

1850

ESP6500EA

AF:

0.369

AC:

3151

ExAC

AF:

0.369

AC:

44643

Asia WGS

AF:

0.396

AC:

1372

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Benign

-0.030

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.1

PhyloP100

2.2

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.27

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.029

Polyphen

1.0

Vest4

0.055

MPC

0.36

ClinPred

0.060

GERP RS

1.4

Varity_R

0.11

gMVP

0.34

Mutation Taster

=97/3

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