rs1788357500

Variant names:

• chr7-48227287-T-A
• rs1788357500
• NM_152701.5:c.494T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152701.5(ABCA13):​c.494T>A​(p.Val165Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ABCA13 NM_152701.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA13	NM_152701.5	c.494T>A	p.Val165Glu	missense_variant	Exon 6 of 62	ENST00000435803.6	NP_689914.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA13	ENST00000435803.6	c.494T>A	p.Val165Glu	missense_variant	Exon 6 of 62	1	NM_152701.5	ENSP00000411096.1
ABCA13	ENST00000417403.5	n.494T>A		non_coding_transcript_exon_variant	Exon 6 of 18	2		ENSP00000409268.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151854 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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.: 32

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151854 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74124

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

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: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.494T>A (p.V165E) alteration is located in exon 6 (coding exon 6) of the ABCA13 gene. This alteration results from a T to A substitution at nucleotide position 494, causing the valine (V) at amino acid position 165 to be replaced by a glutamic acid (E). 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	0.34
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.96
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.42	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.67
MutPred		0.34		Gain of disorder (P = 0.0017);
MVP		0.37
MPC		0.13
ClinPred		0.88	D
GERP RS		4.4
gMVP		0.34

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

Other links and lift over

dbSNP: rs1788357500; hg19: chr7-48266884;