chr7-48234137-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152701.5(ABCA13):​c.883G>A​(p.Ala295Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ABCA13
NM_152701.5 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.638
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.124360085).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCA13NM_152701.5 linkuse as main transcriptc.883G>A p.Ala295Thr missense_variant 8/62 ENST00000435803.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCA13ENST00000435803.6 linkuse as main transcriptc.883G>A p.Ala295Thr missense_variant 8/621 NM_152701.5 P1
ABCA13ENST00000417403.5 linkuse as main transcriptc.883G>A p.Ala295Thr missense_variant, NMD_transcript_variant 8/182 Q86UQ4-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461644
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727098
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 18, 2021The c.883G>A (p.A295T) alteration is located in exon 8 (coding exon 8) of the ABCA13 gene. This alteration results from a G to A substitution at nucleotide position 883, causing the alanine (A) at amino acid position 295 to be replaced by a threonine (T). 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
Benign
0.088
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
19
DANN
Uncertain
1.0
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.44
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.21
Sift
Uncertain
0.011
D
Sift4G
Uncertain
0.033
D
Vest4
0.17
MutPred
0.17
Gain of glycosylation at A295 (P = 0.0564);
MVP
0.64
MPC
0.027
ClinPred
0.42
T
GERP RS
1.3
gMVP
0.038

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-48273734; COSMIC: COSV105937658; API