rs6716901

Variant names:

• chr2-171816943-G-A
• rs6716901
• NM_003705.5:c.931-1741C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003705.5(SLC25A12):​c.931-1741C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0856 in 152,218 control chromosomes in the GnomAD database, including 690 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.086 (690 hom., cov: 30)
• Consequence: SLC25A12 NM_003705.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 9 publications found

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]

SLC25A12 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 39

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A12	NM_003705.5	c.931-1741C>T		intron_variant	Intron 9 of 17	ENST00000422440.7	NP_003696.2
SLC25A12	NR_047549.2	n.845-1741C>T		intron_variant	Intron 8 of 16
SLC25A12	XM_047446142.1	c.658-1741C>T		intron_variant	Intron 7 of 15		XP_047302098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A12	ENST00000422440.7	c.931-1741C>T		intron_variant	Intron 9 of 17	1	NM_003705.5	ENSP00000388658.2
SLC25A12	ENST00000263812.8	n.*551-1741C>T		intron_variant	Intron 8 of 16	2		ENSP00000263812.4
SLC25A12	ENST00000485880.1	n.459-1741C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0855 AC: 13011 AN: 152100 Hom.: 686 Cov.: 30

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0794

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0779

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0856 AC: 13024 AN: 152218 Hom.: 690 Cov.: 30 AF XY: 0.0857 AC XY: 6378 AN XY: 74408

African (AFR) AF: 0.0220 AC: 916 AN: 41556

American (AMR) AF: 0.0799 AC: 1222 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3468

East Asian (EAS) AF: 0.0649 AC: 336 AN: 5174

South Asian (SAS) AF: 0.105 AC: 505 AN: 4816

European-Finnish (FIN) AF: 0.108 AC: 1141 AN: 10580

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8223 AN: 68006

Other (OTH) AF: 0.0790 AC: 167 AN: 2114

Alfa AF: 0.109 Hom.: 1855

Bravo AF: 0.0778

Asia WGS AF: 0.0950 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.16
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6716901; hg19: chr2-172673453;