dbSNP rs774933140: KRTAP4-9:p.Arg41Cys (chr17-41105509-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_001146041.1(KRTAP4-9):c.121C>T(p.Arg41Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,563,906 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000023 ( 1 hom. )

Consequence

KRTAP4-9
NM_001146041.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.78

Publications

1 publications found

Variant links:

Genes affected

KRTAP4-9 (HGNC:18910): (keratin associated protein 4-9) Involved in aging and hair cycle. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP4-9 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=0.2438016).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146041.1. 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
	KRTAP4-9	NM_001146041.1	MANE Select	c.121C>T	p.Arg41Cys	missense	Exon 1 of 1	NP_001139513.1	Q9BYQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-9	ENST00000391415.2	TSL:6 MANE Select	c.121C>T	p.Arg41Cys	missense	Exon 1 of 1	ENSP00000375234.1	Q9BYQ8

Frequencies

GnomAD3 genomes

AF:

0.0000279

AC:

AN:

143418

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000541

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000299

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000242

AC:

AN:

248180

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000225

AC:

AN:

1420488

Hom.:

Cov.:

135

AF XY:

0.0000269

AC XY:

AN XY:

707374

show subpopulations

African (AFR)

AF:

0.0000672

AC:

AN:

29762

American (AMR)

AF:

0.00

AC:

AN:

39308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25286

East Asian (EAS)

AF:

0.00

AC:

AN:

29278

South Asian (SAS)

AF:

0.000201

AC:

AN:

84436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51142

Middle Eastern (MID)

AF:

0.000361

AC:

AN:

5534

European-Non Finnish (NFE)

AF:

0.00000820

AC:

AN:

1097858

Other (OTH)

AF:

0.0000346

AC:

AN:

57884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.0000279

AC:

AN:

143418

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

69992

show subpopulations

African (AFR)

AF:

0.0000541

AC:

AN:

36962

American (AMR)

AF:

0.00

AC:

AN:

13812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.00

AC:

AN:

4266

South Asian (SAS)

AF:

0.00

AC:

AN:

4704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000299

AC:

AN:

66920

Other (OTH)

AF:

0.00

AC:

AN:

1984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.0000113

ExAC

AF:

0.00000835

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

0.25

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

Eigen

Benign

-0.056

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.078

M_CAP

Benign

0.018

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

3.2

PhyloP100

-3.8

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.14

Sift

Uncertain

0.021

Sift4G

Benign

0.085

Polyphen

1.0

Vest4

0.22

MutPred

0.53

Loss of sheet (P = 0.0817)

MVP

0.27

MPC

0.24

ClinPred

0.72

GERP RS

1.2

PromoterAI

0.0023

Neutral

(source)

Varity_R

0.23

gMVP

0.049

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over