dbSNP rs76875855: KRT73:p.Arg3Cys (chr12-52618518-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_175068.3(KRT73):c.7C>T(p.Arg3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000956 in 1,597,616 control chromosomes in the GnomAD database, including 55 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 0.00055 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 49 hom. )

Consequence

KRT73
NM_175068.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.169

Publications

6 publications found

Variant links:

Genes affected

KRT73 (HGNC:28928): (keratin 73) 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 a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT73 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=0.016466051).

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.001 (1445/1445330) while in subpopulation EAS AF = 0.034 (1342/39456). AF 95% confidence interval is 0.0325. There are 49 homozygotes in GnomAdExome4. There are 701 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT73	NM_175068.3 link	c.7C>T	p.Arg3Cys	missense_variant	Exon 1 of 9	ENST00000305748.7	NP_778238.1	Q86Y46-1
KRT73	XM_047428761.1 link	c.7C>T	p.Arg3Cys	missense_variant	Exon 3 of 11		XP_047284717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT73	ENST00000305748.7 link	c.7C>T	p.Arg3Cys	missense_variant	Exon 1 of 9	1	NM_175068.3	ENSP00000307014.3		Q86Y46-1
KRT73	ENST00000546934.1 link	n.32C>T		non_coding_transcript_exon_variant	Exon 1 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000232

AC:

AN:

237038

AF XY:

0.000203

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000914

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000939

Gnomad OTH exome

AF:

0.000348

GnomAD4 exome

AF:

0.00100

AC:

1445

AN:

1445330

Hom.:

Cov.:

AF XY:

0.000978

AC XY:

701

AN XY:

717128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32804

American (AMR)

AF:

0.0000932

AC:

AN:

42906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25252

East Asian (EAS)

AF:

0.0340

AC:

1342

AN:

39456

South Asian (SAS)

AF:

0.000261

AC:

AN:

84234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52900

Middle Eastern (MID)

AF:

0.000204

AC:

AN:

4900

European-Non Finnish (NFE)

AF:

0.0000489

AC:

AN:

1103384

Other (OTH)

AF:

0.000370

AC:

AN:

59494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

163

245

326

408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000545

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0141

AC:

AN:

5174

South Asian (SAS)

AF:

0.000624

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000170

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.35

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.86

MetaRNN

Benign

0.016

MetaSVM

Uncertain

0.25

MutationAssessor

Benign

1.8

PhyloP100

0.17

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.49

Sift

Uncertain

0.021

Sift4G

Uncertain

0.037

Polyphen

1.0

Vest4

0.67

MVP

0.51

MPC

0.69

ClinPred

0.17

GERP RS

4.5

PromoterAI

0.0056

Neutral

(source)

Varity_R

0.25

gMVP

0.39

Mutation Taster

=76/24

polymorphism

(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