rs2070255

chr22-19177965-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005984.5(SLC25A1):c.279T>C(p.Gly93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 1,602,452 control chromosomes in the GnomAD database, including 5,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (444 hom., cov: 33)
  • Exomes 𝑓: 0.077 (4584 hom.)
• Consequence: SLC25A1 NM_005984.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.949

Genes affected

SLC25A1 (HGNC:10979): (solute carrier family 25 member 1) This gene encodes a member of the mitochondrial carrier subfamily of solute carrier proteins. Members of this family include nuclear-encoded transporters that translocate small metabolites across the mitochondrial membrane. This protein regulates the movement of citrate across the inner membranes of the mitochondria. Mutations in this gene have been associated with combined D-2- and L-2-hydroxyglutaric aciduria. Pseudogenes of this gene have been identified on chromosomes 7, 11, 16, and 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 22-19177965-A-G is Benign according to our data. Variant chr22-19177965-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 159908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.949 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A1	NM_005984.5	c.279T>C	p.Gly93=	synonymous_variant	3/9	ENST00000215882.10
SLC25A1	NM_001256534.2	c.300T>C	p.Gly100=	synonymous_variant	2/8
SLC25A1	NM_001287387.2	c.-31T>C		5_prime_UTR_variant	3/9
SLC25A1	NR_046298.3	n.342T>C		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A1	ENST00000215882.10	c.279T>C	p.Gly93=	synonymous_variant	3/9	1	NM_005984.5	P1

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10400 AN: 151678 Hom.: 444 Cov.: 33

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.0387

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.0852

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0948

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0871

GnomAD3 exomes AF: 0.0779 AC: 17379 AN: 222994 Hom.: 717 AF XY: 0.0777 AC XY: 9514 AN XY: 122422

Gnomad AFR exome AF: 0.0389

Gnomad AMR exome AF: 0.0990

Gnomad ASJ exome AF: 0.0845

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.0878

Gnomad FIN exome AF: 0.0443

Gnomad NFE exome AF: 0.0717

Gnomad OTH exome AF: 0.0879

GnomAD4 exome AF: 0.0771 AC: 111869 AN: 1450656 Hom.: 4584 Cov.: 33 AF XY: 0.0774 AC XY: 55778 AN XY: 720924

Gnomad4 AFR exome AF: 0.0442

Gnomad4 AMR exome AF: 0.0979

Gnomad4 ASJ exome AF: 0.0852

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.0887

Gnomad4 FIN exome AF: 0.0469

Gnomad4 NFE exome AF: 0.0756

Gnomad4 OTH exome AF: 0.0763

GnomAD4 genome AF: 0.0685 AC: 10405 AN: 151796 Hom.: 444 Cov.: 33 AF XY: 0.0690 AC XY: 5120 AN XY: 74236

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.0913

Gnomad4 ASJ AF: 0.0852

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0949

Gnomad4 FIN AF: 0.0458

Gnomad4 NFE AF: 0.0766

Gnomad4 OTH AF: 0.0871

Alfa AF: 0.0730 Hom.: 147

Bravo AF: 0.0716

Asia WGS AF: 0.103 AC: 358 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 31, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 02, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	12
Dann	Benign	0.83

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: rs2070255; hg19: chr22-19165478;