Variant 7-48227272-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152701.5(ABCA13):c.479A>G(p.Asn160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,613,334 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000094 ( 1 hom. )

Consequence

ABCA13
NM_152701.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 1.61

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010805011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA13	NM_152701.5 linkuse as main transcript	c.479A>G	p.Asn160Ser	missense_variant	6/62	ENST00000435803.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA13	ENST00000435803.6 linkuse as main transcript	c.479A>G	p.Asn160Ser	missense_variant	6/62	1	NM_152701.5	P1
ABCA13	ENST00000417403.5 linkuse as main transcript	c.479A>G	p.Asn160Ser	missense_variant, NMD_transcript_variant	6/18	2			Q86UQ4-2

Frequencies

GnomAD3 genomes

AF:

0.000855

AC:

130

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00271

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000984

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:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000209

AC:

AN:

249058

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.00245

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000944

AC:

138

AN:

1461188

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.00308

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000848

AC:

129

AN:

152146

Hom.:

Cov.:

AF XY:

0.000847

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00268

Gnomad4 AMR

AF:

0.000982

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000168

Hom.:

Bravo

AF:

0.000854

ESP6500AA

AF:

0.00275

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000232

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.479A>G (p.N160S) alteration is located in exon 6 (coding exon 6) of the ABCA13 gene. This alteration results from a A to G substitution at nucleotide position 479, causing the asparagine (N) at amino acid position 160 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

ABCA13-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 28, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.58

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.58

M_CAP

Benign

0.0033

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

REVEL

Benign

0.016

Sift

Benign

0.20

Sift4G

Benign

0.23

Vest4

0.23

MVP

0.30

MPC

0.057

ClinPred

0.022

GERP RS

1.8

gMVP

0.060

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over