rs6716901

chr2-171816943-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	UniProt
SLC25A12	NM_003705.5	c.931-1741C>T		intron_variant		ENST00000422440.7
SLC25A12	XM_047446142.1	c.658-1741C>T		intron_variant
SLC25A12	NR_047549.2	n.845-1741C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A12	ENST00000422440.7	c.931-1741C>T		intron_variant		1	NM_003705.5	P1
SLC25A12	ENST00000263812.8	c.*551-1741C>T		intron_variant, NMD_transcript_variant		2
SLC25A12	ENST00000485880.1	n.459-1741C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.0799

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0649

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0790

Alfa AF: 0.112 Hom.: 1386

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

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: rs6716901; hg19: chr2-172673453;