7-48239387-G-C

Variant summary

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

The NM_152701.5(ABCA13):c.1044G>C(p.Trp348Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCA13 NM_152701.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

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/exons	MANE	UniProt
ABCA13	NM_152701.5	c.1044G>C	p.Trp348Cys	missense_variant	9/62	ENST00000435803.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA13	ENST00000435803.6	c.1044G>C	p.Trp348Cys	missense_variant	9/62	1	NM_152701.5	P1
ABCA13	ENST00000417403.5	c.*166G>C		3_prime_UTR_variant, NMD_transcript_variant	9/18	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.1044G>C (p.W348C) alteration is located in exon 9 (coding exon 9) of the ABCA13 gene. This alteration results from a G to C substitution at nucleotide position 1044, causing the tryptophan (W) at amino acid position 348 to be replaced by a cysteine (C). 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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
Cadd	Uncertain	25
Dann	Uncertain	0.99
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.40	D
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Vest4		0.35
MutPred		0.60		Loss of MoRF binding (P = 0.0076);
MVP		0.83
MPC		0.15
ClinPred		0.96	D
GERP RS		4.9
gMVP		0.17

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: chr7-48278984;