Genetic Variant KRT77:p.Ser322Phe (chr12-52694741-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.965C>T(p.Ser322Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0384 in 1,612,824 control chromosomes in the GnomAD database, including 1,407 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 0.032 ( 107 hom., cov: 32)

Exomes 𝑓: 0.039 ( 1300 hom. )

Consequence

KRT77
NM_175078.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.63

Publications

14 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=0.008925647).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT77	NM_175078.3 link	c.965C>T	p.Ser322Phe	missense_variant	Exon 5 of 9	ENST00000341809.8	NP_778253.2	Q7Z794Q0IIN1
KRT77	XM_011538288.3 link	c.266C>T	p.Ser89Phe	missense_variant	Exon 5 of 9		XP_011536590.1
KRT77	XM_011538289.3 link	c.*122C>T		splice_region_variant	Exon 5 of 5		XP_011536591.1
KRT77	XM_011538289.3 link	c.*122C>T		3_prime_UTR_variant	Exon 5 of 5		XP_011536591.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT77	ENST00000341809.8 link	c.965C>T	p.Ser322Phe	missense_variant	Exon 5 of 9	1	NM_175078.3	ENSP00000342710.3		Q7Z794

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4835

AN:

152170

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0277

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.00713

Gnomad SAS

AF:

0.0726

Gnomad FIN

AF:

0.0383

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0398

Gnomad OTH

AF:

0.0359

GnomAD2 exomes

AF:

0.0359

AC:

9021

AN:

251228

AF XY:

0.0385

show subpopulations

Gnomad AFR exome

AF:

0.0158

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0302

Gnomad EAS exome

AF:

0.00783

Gnomad FIN exome

AF:

0.0418

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0388

GnomAD4 exome

AF:

0.0390

AC:

57024

AN:

1460536

Hom.:

1300

Cov.:

AF XY:

0.0403

AC XY:

29248

AN XY:

726310

show subpopulations

African (AFR)

AF:

0.0162

AC:

542

AN:

33466

American (AMR)

AF:

0.0187

AC:

834

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.0286

AC:

747

AN:

26112

East Asian (EAS)

AF:

0.00724

AC:

287

AN:

39658

South Asian (SAS)

AF:

0.0685

AC:

5898

AN:

86108

European-Finnish (FIN)

AF:

0.0417

AC:

2226

AN:

53390

Middle Eastern (MID)

AF:

0.0576

AC:

332

AN:

5766

European-Non Finnish (NFE)

AF:

0.0396

AC:

43979

AN:

1111014

Other (OTH)

AF:

0.0361

AC:

2179

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

2676

5352

8029

10705

13381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1646

3292

4938

6584

8230

<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:

0.0317

AC:

4835

AN:

152288

Hom.:

107

Cov.:

AF XY:

0.0331

AC XY:

2461

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0174

AC:

723

AN:

41566

American (AMR)

AF:

0.0277

AC:

424

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3470

East Asian (EAS)

AF:

0.00715

AC:

AN:

5174

South Asian (SAS)

AF:

0.0735

AC:

355

AN:

4830

European-Finnish (FIN)

AF:

0.0383

AC:

406

AN:

10608

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0398

AC:

2710

AN:

68016

Other (OTH)

AF:

0.0360

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

240

479

719

958

1198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0368

Hom.:

318

Bravo

AF:

0.0278

TwinsUK

AF:

0.0356

AC:

132

ALSPAC

AF:

0.0449

AC:

173

ESP6500AA

AF:

0.0163

AC:

ESP6500EA

AF:

0.0399

AC:

343

ExAC

AF:

0.0364

AC:

4421

Asia WGS

AF:

0.0340

AC:

117

AN:

3478

EpiCase

AF:

0.0395

EpiControl

AF:

0.0406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0089

MetaSVM

Uncertain

0.58

MutationAssessor

Pathogenic

4.1

PhyloP100

3.6

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.17

MPC

0.78

ClinPred

0.086

GERP RS

4.8

Varity_R

0.91

gMVP

0.32

Mutation Taster

=83/17

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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