2-171785278-T-C

Variant names:

• chr2-171785278-T-C
• NM_003705.5:c.2033A>G

Variant summary

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

The NM_003705.5(SLC25A12):​c.2033A>G​(p.Gln678Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC25A12 NM_003705.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

Genes affected

SLC25A12 (HGNC:10982): (solute carrier family 25 member 12) This gene encodes a calcium-binding mitochondrial carrier protein. The encoded protein localizes to the mitochondria and is involved in the exchange of aspartate for glutamate across the inner mitochondrial membrane. Polymorphisms in this gene may be associated with autism, and mutations in this gene may also be a cause of global cerebral hypomyelination. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Apr 2012]

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=0.1522876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A12	NM_003705.5	c.2033A>G	p.Gln678Arg	missense_variant	Exon 18 of 18	ENST00000422440.7	NP_003696.2
SLC25A12	XM_047446142.1	c.1760A>G	p.Gln587Arg	missense_variant	Exon 16 of 16		XP_047302098.1
SLC25A12	NR_047549.2	n.1947A>G		non_coding_transcript_exon_variant	Exon 17 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A12	ENST00000422440.7	c.2033A>G	p.Gln678Arg	missense_variant	Exon 18 of 18	1	NM_003705.5	ENSP00000388658.2
SLC25A12	ENST00000263812.8	n.*1653A>G		non_coding_transcript_exon_variant	Exon 17 of 17	2		ENSP00000263812.4
SLC25A12	ENST00000472070.1	n.1443A>G		non_coding_transcript_exon_variant	Exon 3 of 3	2
SLC25A12	ENST00000263812.8	n.*1653A>G		3_prime_UTR_variant	Exon 17 of 17	2		ENSP00000263812.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.037
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.22	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.17
MutPred		0.27		Gain of methylation at Q678 (P = 0.015);
MVP		0.55
MPC		0.69
ClinPred		0.49	T
GERP RS		4.9
Varity_R		0.21
gMVP		0.56

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: chr2-172641788;