rs726070

Positions:

• chr2-214948607-C-A
• chr2-214948607-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PM5 BP4

The ENST00000272895.12(ABCA12):​c.7093G>T​(p.Asp2365Tyr) 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. 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. D2365N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABCA12 ENST00000272895.12 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53

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]

SNHG31 (HGNC:54196): (small nucleolar RNA host gene 31)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr2-214948607-C-T is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.4136606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA12	NM_173076.3	c.7093G>T	p.Asp2365Tyr	missense_variant	47/53	ENST00000272895.12	NP_775099.2
SNHG31	NR_110292.1	n.444+660C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12	c.7093G>T	p.Asp2365Tyr	missense_variant	47/53	1	NM_173076.3	ENSP00000272895	P1
SNHG31	ENST00000670391.1	n.438-13203C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	26
DANN	Benign	0.97
DEOGEN2	Uncertain	0.70	D;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.9	N;N
REVEL	Pathogenic	0.68
Sift	Benign	0.20	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.97	D;B
Vest4		0.50
MutPred		0.60		Loss of ubiquitination at K2364 (P = 0.0369);.;
MVP		0.92
MPC		0.77
ClinPred		0.85	D
GERP RS		4.6
Varity_R		0.23
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs726070; hg19: chr2-215813331;