Genetic Variant NM_002278.3:c.1163G>A (chr17-41462884-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002278.3(KRT32):c.1163G>A(p.Arg388Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000379 in 1,582,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

KRT32
NM_002278.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18

Publications

0 publications found

Variant links:

Genes affected

KRT32 (HGNC:6449): (keratin 32) The protein encoded by this gene is a member of the keratin gene family. As a type I hair keratin, it 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]

KRT32 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24911326).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002278.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT32	NM_002278.3	MANE Select	c.1163G>A	p.Arg388Gln	missense	Exon 6 of 7	NP_002269.3	Q14532

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT32	ENST00000225899.4	TSL:1 MANE Select	c.1163G>A	p.Arg388Gln	missense	Exon 6 of 7	ENSP00000225899.3	Q14532

Frequencies

GnomAD3 genomes

AF:

0.0000422

AC:

AN:

142054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00114

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000680

AC:

AN:

250090

AF XY:

0.0000962

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000375

AC:

AN:

1440288

Hom.:

Cov.:

AF XY:

0.0000489

AC XY:

AN XY:

715762

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32946

American (AMR)

AF:

0.00

AC:

AN:

43400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25634

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38564

South Asian (SAS)

AF:

0.000452

AC:

AN:

81856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5588

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

1100078

Other (OTH)

AF:

0.0000337

AC:

AN:

59382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000422

AC:

AN:

142172

Hom.:

Cov.:

AF XY:

0.0000573

AC XY:

AN XY:

69824

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38556

American (AMR)

AF:

0.00

AC:

AN:

14318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3218

East Asian (EAS)

AF:

0.00

AC:

AN:

4750

South Asian (SAS)

AF:

0.00114

AC:

AN:

4370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

252

European-Non Finnish (NFE)

AF:

0.0000157

AC:

AN:

63604

Other (OTH)

AF:

0.00

AC:

AN:

1928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.043

MetaRNN

Benign

0.25

MetaSVM

Pathogenic

0.88

MutationAssessor

Uncertain

2.6

PhyloP100

4.2

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.57

Sift

Benign

0.031

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.41

MutPred

0.63

Loss of stability (P = 0.1829)

MVP

0.82

MPC

0.16

ClinPred

0.76

GERP RS

5.1

Varity_R

0.28

gMVP

0.41

Mutation Taster

=82/18

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over