chr17-81715496-C-G

Position:

• chr17-81715496-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_012140.5(SLC25A10):​c.232C>G​(p.Arg78Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A10 NM_012140.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25

Genes affected

SLC25A10 (HGNC:10980): (solute carrier family 25 member 10) This gene encodes a member of a family of proteins that translocate small metabolites across the mitochondrial membrane. The encoded protein exchanges dicarboxylates, such as malate and succinate, for phosphate, sulfate, and other small molecules, thereby providing substrates for metabolic processes including the Krebs cycle and fatty acid synthesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

ENSG00000262660 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.947

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A10	NM_012140.5	c.232C>G	p.Arg78Gly	missense_variant	3/11	ENST00000350690.10	NP_036272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A10	ENST00000350690.10	c.232C>G	p.Arg78Gly	missense_variant	3/11	1	NM_012140.5	ENSP00000345580.5
ENSG00000262660	ENST00000571730.1	c.697C>G	p.Arg233Gly	missense_variant	7/15	2		ENSP00000461324.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.232C>G (p.R78G) alteration is located in exon 3 (coding exon 3) of the SLC25A10 gene. This alteration results from a C to G substitution at nucleotide position 232, causing the arginine (R) at amino acid position 78 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	.;.;.;D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.95	D;D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Pathogenic	4.0	.;.;H;H
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-6.8	.;.;D;D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.019	.;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.96, 0.97	.;.;D;D
Vest4		0.96
MutPred		0.75		Loss of MoRF binding (P = 0.0443);.;.;.;
MVP		0.89
MPC		0.94
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.84
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79682526;