dbSNP rs566894266: ABCA13:p.Arg44His (chr7-48193020-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152701.5(ABCA13):c.131G>A(p.Arg44His) variant causes a missense change. The variant allele was found at a frequency of 0.0000301 in 1,527,832 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 1 hom. )

Consequence

ABCA13
NM_152701.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.10

Publications

0 publications found

Variant links:

Genes affected

ABCA13 (HGNC:14638): (ATP binding cassette subfamily A member 13) In human, the ATP-binding cassette (ABC) family of transmembrane transporters has at least 48 genes and 7 gene subfamilies. This gene is a member of ABC gene subfamily A (ABCA). Genes within the ABCA family typically encode several thousand amino acids. Like other ABC transmembrane transporter proteins, this protein has 12 or more transmembrane alpha-helix domains that likely arrange to form a single central chamber with multiple substrate binding sites. It is also predicted to have two large extracellular domains and two nucleotide binding domains as is typical for ABCA proteins. Alternative splice variants have been described but their biological validity has not been demonstrated.[provided by RefSeq, Mar 2009]

ABCA13 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ABCA13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.858

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152701.5. 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
	ABCA13	NM_152701.5	MANE Select	c.131G>A	p.Arg44His	missense	Exon 2 of 62	NP_689914.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA13	ENST00000435803.6	TSL:1 MANE Select	c.131G>A	p.Arg44His	missense	Exon 2 of 62	ENSP00000411096.1
	ABCA13	ENST00000417403.5	TSL:2	n.131G>A		non_coding_transcript_exon	Exon 2 of 18	ENSP00000409268.1	Q86UQ4-2

Frequencies

GnomAD3 genomes

AF:

0.0000336

AC:

AN:

148698

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000202

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000795

AC:

AN:

138436

AF XY:

0.0000809

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000248

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000305

AC:

AN:

1379032

Hom.:

Cov.:

AF XY:

0.0000338

AC XY:

AN XY:

680266

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31296

American (AMR)

AF:

0.000198

AC:

AN:

35314

Ashkenazi Jewish (ASJ)

AF:

0.000120

AC:

AN:

25002

East Asian (EAS)

AF:

0.00

AC:

AN:

35316

South Asian (SAS)

AF:

0.000167

AC:

AN:

78058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34872

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.0000130

AC:

AN:

1075842

Other (OTH)

AF:

0.0000694

AC:

AN:

57652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.0000269

AC:

AN:

148800

Hom.:

Cov.:

AF XY:

0.0000553

AC XY:

AN XY:

72270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40332

American (AMR)

AF:

0.000202

AC:

AN:

14886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5078

South Asian (SAS)

AF:

0.00

AC:

AN:

4736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67472

Other (OTH)

AF:

0.00

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000359

Hom.:

Bravo

AF:

0.0000680

ClinVar

ClinVar submissions as Germline

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

0.50

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.43

MetaRNN

Pathogenic

0.86

MetaSVM

Pathogenic

1.1

PhyloP100

5.1

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.9

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.72

MutPred

0.55

Gain of catalytic residue at L43 (P = 0.1593)

MVP

0.93

MPC

0.22

ClinPred

0.87

GERP RS

5.3

gMVP

0.62

Mutation Taster

=95/5

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over