Genetic Variant NM_005553.4:c.133G>A (chr11-71548790-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005553.4(KRTAP5-9):c.133G>A(p.Val45Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,612,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

KRTAP5-9
NM_005553.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0340

Publications

0 publications found

Variant links:

Genes affected

KRTAP5-9 (HGNC:23604): (keratin associated protein 5-9) Enables identical protein binding activity. Predicted to be involved in epidermis development. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.104659855).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005553.4. 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
	KRTAP5-9	NM_005553.4	MANE Select	c.133G>A	p.Val45Met	missense	Exon 1 of 1	NP_005544.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-9	ENST00000528743.4	TSL:6 MANE Select	c.133G>A	p.Val45Met	missense	Exon 1 of 1	ENSP00000431443.3	P26371

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151670

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251394

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461262

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

726944

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33460

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.000651

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5510

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1111752

Other (OTH)

AF:

0.000149

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.0000396

AC:

AN:

151670

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74066

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41264

American (AMR)

AF:

0.0000655

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4776

European-Finnish (FIN)

AF:

0.0000948

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67894

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.000158

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000576

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

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.9

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.064

Eigen

Benign

0.12

Eigen_PC

Benign

-0.054

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.34

M_CAP

Benign

0.00064

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

PhyloP100

-0.034

PROVEAN

Benign

-0.80

REVEL

Benign

0.053

Sift

Benign

0.060

Sift4G

Benign

0.12

Polyphen

0.99

Vest4

0.16

MVP

0.52

MPC

0.095

ClinPred

0.076

GERP RS

1.6

PromoterAI

-0.032

Neutral

(source)

Varity_R

0.028

Mutation Taster

=99/1

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