rs7560008

Positions:

• chr2-215011442-A-C
• chr2-215011442-A-G
• chr2-215011442-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173076.3(ABCA12):​c.2329T>G​(p.Ser777Ala) 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. 15/21 in silico tools predict a benign 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. S777T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCA12 NM_173076.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

ABCA12 (HGNC:14637): (ATP binding cassette subfamily A member 12) 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, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

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=0.07448596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA12	NM_173076.3	c.2329T>G	p.Ser777Ala	missense_variant	17/53	ENST00000272895.12
ABCA12	NM_015657.4	c.1375T>G	p.Ser459Ala	missense_variant	9/45
ABCA12	XM_011510951.3	c.2329T>G	p.Ser777Ala	missense_variant	17/53
ABCA12	NR_103740.2	n.2771T>G		non_coding_transcript_exon_variant	18/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA12	ENST00000272895.12	c.2329T>G	p.Ser777Ala	missense_variant	17/53	1	NM_173076.3	P1
ABCA12	ENST00000389661.4	c.1375T>G	p.Ser459Ala	missense_variant	9/45	1
	ENST00000617699.1	n.29-1614A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.049
DANN	Benign	0.58
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.29	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.021
Sift	Benign	0.36	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0	B;B
Vest4		0.044
MutPred		0.34		Loss of helix (P = 0.2662);.;
MVP		0.22
MPC		0.15
ClinPred		0.065	T
GERP RS		-2.9
Varity_R		0.047
gMVP		0.35

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: rs7560008; hg19: chr2-215876166;