dbSNP rs201561034: KRTAP9-8:p.Pro108Arg (chr17-41238374-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_031963.3(KRTAP9-8):c.323C>G(p.Pro108Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000829 in 1,607,406 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00094 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00082 ( 2 hom. )

Consequence

KRTAP9-8
NM_031963.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Publications

2 publications found

Variant links:

Genes affected

KRTAP9-8 (HGNC:17231): (keratin associated protein 9-8) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

KRTAP9-8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09589189).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031963.3. 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
	KRTAP9-8	NM_031963.3	MANE Select	c.323C>G	p.Pro108Arg	missense	Exon 1 of 1	NP_114169.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP9-8	ENST00000254072.7	TSL:6 MANE Select	c.323C>G	p.Pro108Arg	missense	Exon 1 of 1	ENSP00000254072.6	Q9BYQ0

Frequencies

GnomAD3 genomes

AF:

0.000943

AC:

139

AN:

147424

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000108

Gnomad AMI

AF:

0.00549

Gnomad AMR

AF:

0.00270

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000927

Gnomad OTH

AF:

0.000489

GnomAD2 exomes

AF:

0.000806

AC:

202

AN:

250610

AF XY:

0.000730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000817

AC:

1193

AN:

1459870

Hom.:

Cov.:

AF XY:

0.000778

AC XY:

565

AN XY:

726376

show subpopulations

African (AFR)

AF:

0.0000949

AC:

AN:

31604

American (AMR)

AF:

0.00121

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00256

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00129

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000842

AC:

936

AN:

1111972

Other (OTH)

AF:

0.000995

AC:

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

198

298

397

496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.000942

AC:

139

AN:

147536

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

72142

show subpopulations

African (AFR)

AF:

0.000108

AC:

AN:

37044

American (AMR)

AF:

0.00270

AC:

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.00404

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000927

AC:

AN:

67988

Other (OTH)

AF:

0.000484

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.00115

Hom.:

Bravo

AF:

0.00101

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000702

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.00124

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

Uncertain

0.34

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

Eigen

Benign

-0.073

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.66

M_CAP

Benign

0.0018

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

PhyloP100

1.3

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.088

Sift

Uncertain

0.022

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.72

MVP

0.088

MPC

0.84

ClinPred

0.23

GERP RS

2.2

PromoterAI

0.00090

Neutral

(source)

Varity_R

0.17

gMVP

0.099

Mutation Taster

=99/1

polymorphism

(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

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