3-66262051-G-C

Variant names:

• chr3-66262051-G-C
• NM_001379210.1:c.301G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001379210.1(SLC25A26):​c.301G>C​(p.Val101Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000711 in 1,405,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SLC25A26 NM_001379210.1 missense, splice_region
• Scores: Splicing: ADA: 0.2680
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.60

Genes affected

SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A26	NM_001379210.1	c.301G>C	p.Val101Leu	missense_variant, splice_region_variant	Exon 4 of 10	ENST00000354883.11	NP_001366139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A26	ENST00000354883.11	c.301G>C	p.Val101Leu	missense_variant, splice_region_variant	Exon 4 of 10	2	NM_001379210.1	ENSP00000346955.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1405808 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 696308

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.6	N;N;.
REVEL	Benign	0.29
Sift	Benign	0.19	T;T;.
Sift4G	Benign	0.24	T;T;T
Polyphen		0.0060	B;.;.
Vest4		0.54
MutPred		0.51		Gain of stability (P = 0.1848);.;.;
MVP		0.34
MPC		0.025
ClinPred		0.73	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.27
dbscSNV1_RF	Benign	0.64
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-66312475;