2-171793735-T-G

Variant names:

• chr2-171793735-T-G
• rs149278617
• NM_003705.5:c.1338A>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003705.5(SLC25A12):​c.1338A>C​(p.Pro446Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,614,048 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (16 hom.)
• Consequence: SLC25A12 NM_003705.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.50

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-171793735-T-G is Benign according to our data. Variant chr2-171793735-T-G is described in ClinVar as [Benign]. Clinvar id is 332340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.5 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0057 (868/152176) while in subpopulation AFR AF= 0.0177 (734/41512). AF 95% confidence interval is 0.0166. There are 4 homozygotes in gnomad4. There are 429 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A12	NM_003705.5	c.1338A>C	p.Pro446Pro	synonymous_variant	Exon 14 of 18	ENST00000422440.7	NP_003696.2
SLC25A12	XM_047446142.1	c.1065A>C	p.Pro355Pro	synonymous_variant	Exon 12 of 16		XP_047302098.1
SLC25A12	NR_047549.2	n.1252A>C		non_coding_transcript_exon_variant	Exon 13 of 17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A12	ENST00000422440.7	c.1338A>C	p.Pro446Pro	synonymous_variant	Exon 14 of 18	1	NM_003705.5	ENSP00000388658.2
SLC25A12	ENST00000263812.8	n.*958A>C		non_coding_transcript_exon_variant	Exon 13 of 17	2		ENSP00000263812.4
SLC25A12	ENST00000263812.8	n.*958A>C		3_prime_UTR_variant	Exon 13 of 17	2		ENSP00000263812.4

Frequencies

GnomAD3 genomes AF: 0.00571 AC: 868 AN: 152058 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000574

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00181 AC: 456 AN: 251250 Hom.: 4 AF XY: 0.00137 AC XY: 186 AN XY: 135786

Gnomad AFR exome AF: 0.0161

Gnomad AMR exome AF: 0.00327

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000493

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.000993 AC: 1452 AN: 1461872 Hom.: 16 Cov.: 32 AF XY: 0.000913 AC XY: 664 AN XY: 727234

Gnomad4 AFR exome AF: 0.0199

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.000727

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000332

Gnomad4 OTH exome AF: 0.00321

GnomAD4 genome AF: 0.00570 AC: 868 AN: 152176 Hom.: 4 Cov.: 32 AF XY: 0.00577 AC XY: 429 AN XY: 74396

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000574

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00101 Hom.: 1

Bravo AF: 0.00660

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 31, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SLC25A12-related disorder Benign:1

Mar 03, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.20
DANN	Benign	0.53

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: rs149278617; hg19: chr2-172650245;