dbSNP rs375827401: KRTAP4-1:p.Arg133His (chr17-41184457-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_001386841.1(KRTAP4-1):c.398G>A(p.Arg133His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000941 in 1,604,558 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000099 ( 1 hom. )

Consequence

KRTAP4-1
NM_001386841.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.512

Publications

0 publications found

Variant links:

Genes affected

KRTAP4-1 (HGNC:18907): (keratin associated protein 4-1) 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]

KRTAP4-1 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=0.0815047).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386841.1. 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
	KRTAP4-1	NM_001386841.1	MANE Select	c.398G>A	p.Arg133His	missense	Exon 1 of 1	NP_001373770.1	Q9BYQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-1	ENST00000398472.2	TSL:6 MANE Select	c.398G>A	p.Arg133His	missense	Exon 1 of 1	ENSP00000381489.1	Q9BYQ7

Frequencies

GnomAD3 genomes

AF:

0.0000465

AC:

AN:

150616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000734

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:

0.0000592

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000653

AC:

AN:

245058

AF XY:

0.0000452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000494

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000539

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000990

AC:

144

AN:

1453942

Hom.:

Cov.:

163

AF XY:

0.000103

AC XY:

AN XY:

721902

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33308

American (AMR)

AF:

0.0000226

AC:

AN:

44234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25802

East Asian (EAS)

AF:

0.000405

AC:

AN:

39494

South Asian (SAS)

AF:

0.00

AC:

AN:

85672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.000107

AC:

118

AN:

1106588

Other (OTH)

AF:

0.0000666

AC:

AN:

60030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.0000465

AC:

AN:

150616

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

73530

show subpopulations

African (AFR)

AF:

0.0000734

AC:

AN:

40892

American (AMR)

AF:

0.00

AC:

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000592

AC:

AN:

67586

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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:

0.0000712

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000330

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

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.088

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.051

M_CAP

Benign

0.0021

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.90

PhyloP100

-0.51

PrimateAI

Benign

0.18

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.025

Sift

Benign

0.081

Sift4G

Benign

0.075

Polyphen

0.44

Vest4

0.11

MVP

0.030

MPC

0.20

ClinPred

0.052

GERP RS

3.2

PromoterAI

0.0032

Neutral

(source)

Varity_R

0.066

gMVP

0.056

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

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