Genetic Variant ABCA13:p.Lys161Asn (chr7-48227276-G-T) – 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_152701.5(ABCA13):c.483G>T(p.Lys161Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 0.0 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

ABCA13
NM_152701.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0990

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:

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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=0.16286272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA13	NM_152701.5 link	c.483G>T	p.Lys161Asn	missense_variant	Exon 6 of 62	ENST00000435803.6	NP_689914.3	Q86UQ4A0A0A0MT16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA13	ENST00000435803.6 link	c.483G>T	p.Lys161Asn	missense_variant	Exon 6 of 62	1	NM_152701.5	ENSP00000411096.1		A0A0A0MT16
ABCA13	ENST00000417403.5 link	n.483G>T		non_coding_transcript_exon_variant	Exon 6 of 18	2		ENSP00000409268.1		Q86UQ4-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151768

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

151768

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74078

African (AFR)

AF:

0.00

AC:

AN:

41278

American (AMR)

AF:

0.00

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2086

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 03, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.483G>T (p.K161N) alteration is located in exon 6 (coding exon 6) of the ABCA13 gene. This alteration results from a G to T substitution at nucleotide position 483, causing the lysine (K) at amino acid position 161 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.52

M_CAP

Benign

0.0075

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

PhyloP100

0.099

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.2

REVEL

Benign

0.097

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Vest4

0.23

MutPred

0.30

Loss of ubiquitination at K161 (P = 0.013);

MVP

0.36

MPC

0.11

ClinPred

0.80

GERP RS

-3.0

gMVP

0.11

Mutation Taster

=91/9

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over