Genetic Variant NM_033184.4:c.151A>G (chr17-41065695-T-C) – 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_033184.4(KRTAP2-4):c.151A>G(p.Thr51Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000814 in 1,474,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

KRTAP2-4
NM_033184.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Publications

0 publications found

Variant links:

Genes affected

KRTAP2-4 (HGNC:18891): (keratin associated protein 2-4) 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 high sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

KRTAP2-4 links:

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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=0.10325411).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033184.4. 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
	KRTAP2-4	NM_033184.4	MANE Select	c.151A>G	p.Thr51Ala	missense	Exon 1 of 1	NP_149440.1	Q9BYR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP2-4	ENST00000394015.3	TSL:6 MANE Select	c.151A>G	p.Thr51Ala	missense	Exon 1 of 1	ENSP00000377583.2	Q9BYR9

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150800

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:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000112

AC:

AN:

80674

AF XY:

0.0000957

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000959

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000831

AC:

AN:

1323970

Hom.:

Cov.:

AF XY:

0.00000618

AC XY:

AN XY:

647076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30332

American (AMR)

AF:

0.00

AC:

AN:

29764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21148

East Asian (EAS)

AF:

0.000312

AC:

AN:

35246

South Asian (SAS)

AF:

0.00

AC:

AN:

69608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3808

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047292

Other (OTH)

AF:

0.00

AC:

AN:

55188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00000663

AC:

AN:

150800

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41032

American (AMR)

AF:

0.00

AC:

AN:

15144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.000195

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67548

Other (OTH)

AF:

0.00

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

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

0.19

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.82

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.98

PhyloP100

1.8

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.32

REVEL

Benign

0.14

Sift

Benign

0.16

Sift4G

Uncertain

0.013

Vest4

0.13

MutPred

0.37

Loss of phosphorylation at T51 (P = 0.0457)

MVP

0.34

MPC

1.5

ClinPred

0.22

GERP RS

5.5

PromoterAI

0.060

Neutral

(source)

Varity_R

0.067

gMVP

0.048

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over