rs145087575

Positions:

• chr16-2324484-C-G
• chr16-2324484-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001089.3(ABCA3):​c.367G>C​(p.Asp123His) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D123N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABCA3 NM_001089.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940

Genes affected

ABCA3 (HGNC:33): (ATP binding cassette subfamily A member 3) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. The full transporter encoded by this gene may be involved in development of resistance to xenobiotics and engulfment during programmed cell death. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA3	NM_001089.3	c.367G>C	p.Asp123His	missense_variant	6/33	ENST00000301732.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA3	ENST00000301732.10	c.367G>C	p.Asp123His	missense_variant	6/33	1	NM_001089.3	P1
ABCA3	ENST00000382381.7	c.367G>C	p.Asp123His	missense_variant	6/32	1
ABCA3	ENST00000567910.1	c.367G>C	p.Asp123His	missense_variant	5/6	1
ABCA3	ENST00000563623.5	n.930G>C		non_coding_transcript_exon_variant	6/20	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.55	D;.;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.9	L;.;L
MutationTaster	Benign	0.89	D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.7	D;N;D
REVEL	Uncertain	0.59
Sift	Benign	0.056	T;T;D
Sift4G	Benign	0.17	T;T;D
Polyphen		0.28	B;.;.
Vest4		0.76
MutPred		0.53		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.86
MPC		0.46
ClinPred		0.53	D
GERP RS		2.4
Varity_R		0.11
gMVP		0.81

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: rs145087575; hg19: chr16-2374485;