rs2070255

Variant names:

• chr22-19177965-A-G
• rs2070255
• NM_005984.5:c.279T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005984.5(SLC25A1):​c.279T>C​(p.Gly93Gly) 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:5
• Conservation: PhyloP100: 0.949
• Publications: 12 publications found

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]

LINC01311 (HGNC:50503): (long intergenic non-protein coding RNA 1311)

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
SLC25A1	NM_005984.5	c.279T>C	p.Gly93Gly	synonymous_variant	Exon 3 of 9	ENST00000215882.10	NP_005975.1
SLC25A1	NM_001256534.2	c.300T>C	p.Gly100Gly	synonymous_variant	Exon 2 of 8		NP_001243463.1
SLC25A1	NR_046298.3	n.342T>C		non_coding_transcript_exon_variant	Exon 3 of 8
SLC25A1	NM_001287387.2	c.-31T>C		5_prime_UTR_variant	Exon 3 of 9		NP_001274316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A1	ENST00000215882.10	c.279T>C	p.Gly93Gly	synonymous_variant	Exon 3 of 9	1	NM_005984.5	ENSP00000215882.5

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

GnomAD2 exomes AF: 0.0779 AC: 17379 AN: 222994 AF XY: 0.0777

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 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

African (AFR) AF: 0.0442 AC: 1474 AN: 33386

American (AMR) AF: 0.0979 AC: 4219 AN: 43108

Ashkenazi Jewish (ASJ) AF: 0.0852 AC: 2202 AN: 25832

East Asian (EAS) AF: 0.128 AC: 5018 AN: 39256

South Asian (SAS) AF: 0.0887 AC: 7516 AN: 84764

European-Finnish (FIN) AF: 0.0469 AC: 2383 AN: 50822

Middle Eastern (MID) AF: 0.125 AC: 642 AN: 5128

European-Non Finnish (NFE) AF: 0.0756 AC: 83847 AN: 1108456

Other (OTH) AF: 0.0763 AC: 4568 AN: 59904

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

African (AFR) AF: 0.0413 AC: 1712 AN: 41420

American (AMR) AF: 0.0913 AC: 1395 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0852 AC: 295 AN: 3464

East Asian (EAS) AF: 0.118 AC: 600 AN: 5104

South Asian (SAS) AF: 0.0949 AC: 457 AN: 4816

European-Finnish (FIN) AF: 0.0458 AC: 483 AN: 10550

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.0766 AC: 5194 AN: 67850

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0724 Hom.: 147

Bravo AF: 0.0716

Asia WGS AF: 0.103 AC: 358 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 02, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:2

Oct 31, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 04, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.95
Mutation Taster		=291/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2070255; hg19: chr22-19165478;