rs142891505

Variant names:

• chr2-171787612-A-G
• rs142891505
• NM_003705.5:c.1794T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-171787612-A-G
• chr2-171787612-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003705.5(SLC25A12):​c.1794T>C​(p.Tyr598Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000372 in 1,614,202 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: SLC25A12 NM_003705.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0370
• Publications: 1 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 2-171787612-A-G is Benign according to our data. Variant chr2-171787612-A-G is described in ClinVar as Benign. ClinVar VariationId is 414024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.037 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00167 (254/152336) while in subpopulation AFR AF = 0.0058 (241/41578). AF 95% confidence interval is 0.0052. There are 1 homozygotes in GnomAd4. There are 121 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003705.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A12	NM_003705.5	MANE Select	c.1794T>C	p.Tyr598Tyr	synonymous	Exon 17 of 18	NP_003696.2
	SLC25A12	NR_047549.2		n.1708T>C		non_coding_transcript_exon	Exon 16 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A12	ENST00000422440.7	TSL:1 MANE Select	c.1794T>C	p.Tyr598Tyr	synonymous	Exon 17 of 18	ENSP00000388658.2	O75746-1
	SLC25A12	ENST00000958780.1		c.1971T>C	p.Tyr657Tyr	synonymous	Exon 19 of 20	ENSP00000628839.1
	SLC25A12	ENST00000958781.1		c.1881T>C	p.Tyr627Tyr	synonymous	Exon 18 of 19	ENSP00000628840.1

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 249 AN: 152218 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000481 AC: 121 AN: 251430 AF XY: 0.000353

Gnomad AFR exome AF: 0.00535

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000237 AC: 347 AN: 1461866 Hom.: 2 Cov.: 31 AF XY: 0.000245 AC XY: 178 AN XY: 727238

African (AFR) AF: 0.00648 AC: 217 AN: 33480

American (AMR) AF: 0.000425 AC: 19 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.000406 AC: 35 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111994

Other (OTH) AF: 0.000828 AC: 50 AN: 60392

GnomAD4 genome AF: 0.00167 AC: 254 AN: 152336 Hom.: 1 Cov.: 32 AF XY: 0.00162 AC XY: 121 AN XY: 74488

African (AFR) AF: 0.00580 AC: 241 AN: 41578

American (AMR) AF: 0.000392 AC: 6 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000620 Hom.: 2

Bravo AF: 0.00193

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	SLC25A12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.1
DANN	Benign	0.67
PhyloP100		0.037
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142891505; hg19: chr2-172644122;