rs535710884

Positions:

• chr2-171810285-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003705.5(SLC25A12):​c.1172-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,611,888 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (4 hom.)
• Consequence: SLC25A12 NM_003705.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.540

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 -10 ACMG points.

• BP6: Variant 2-171810285-AG-A is Benign according to our data. Variant chr2-171810285-AG-A is described in ClinVar as [Benign]. Clinvar id is 239550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00112 (171/152290) while in subpopulation NFE AF= 0.00134 (91/68022). AF 95% confidence interval is 0.00112. There are 1 homozygotes in gnomad4. There are 108 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A12	NM_003705.5	c.1172-10del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000422440.7	NP_003696.2
SLC25A12	XM_047446142.1	c.899-10del		splice_polypyrimidine_tract_variant, intron_variant			XP_047302098.1
SLC25A12	NR_047549.2	n.1086-10del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A12	ENST00000422440.7	c.1172-10del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003705.5	ENSP00000388658	P1
SLC25A12	ENST00000263812.8	c.*792-10del		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2		ENSP00000263812
SLC25A12	ENST00000494892.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 171 AN: 152172 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00669

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00150 AC: 377 AN: 251404 Hom.: 1 AF XY: 0.00149 AC XY: 202 AN XY: 135884

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00596

Gnomad NFE exome AF: 0.00191

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00110 AC: 1612 AN: 1459598 Hom.: 4 Cov.: 29 AF XY: 0.00106 AC XY: 768 AN XY: 726314

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00599

Gnomad4 NFE exome AF: 0.00109

Gnomad4 OTH exome AF: 0.000928

GnomAD4 genome AF: 0.00112 AC: 171 AN: 152290 Hom.: 1 Cov.: 32 AF XY: 0.00145 AC XY: 108 AN XY: 74456

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00669

Gnomad4 NFE AF: 0.00134

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000982 Hom.: 0

Bravo AF: 0.000514

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 21, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 08, 2016	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs535710884; hg19: chr2-172666795;