17-81712445-G-A

Position:

• chr17-81712445-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012140.5(SLC25A10):​c.19G>A​(p.Val7Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000173 in 1,154,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: SLC25A10 NM_012140.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3339364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A10	NM_012140.5	c.19G>A	p.Val7Met	missense_variant	1/11	ENST00000350690.10	NP_036272.2
SLC25A10	NM_001270953.2	c.19G>A	p.Val7Met	missense_variant	1/11		NP_001257882.1
SLC25A10	NM_001270888.2	c.19G>A	p.Val7Met	missense_variant	1/11		NP_001257817.1
SLC25A10	XM_047435431.1	c.19G>A	p.Val7Met	missense_variant	1/10		XP_047291387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A10	ENST00000350690.10	c.19G>A	p.Val7Met	missense_variant	1/11	1	NM_012140.5	ENSP00000345580.5
ENSG00000262660	ENST00000571730.1	c.571-2520G>A		intron_variant		2		ENSP00000461324.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000173 AC: 2 AN: 1154818 Hom.: 0 Cov.: 30 AF XY: 0.00000178 AC XY: 1 AN XY: 560934

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: 0.00000208

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Nov 12, 2021

The c.19G>A (p.V7M) alteration is located in exon 1 (coding exon 1) of the SLC25A10 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the valine (V) at amino acid position 7 to be replaced by a methionine (M). 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	Uncertain	0.39
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.097
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.8	.;L;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.81	.;N;N
REVEL	Benign	0.20
Sift	Benign	0.059	.;T;T
Sift4G	Uncertain	0.026	D;T;T
Polyphen		0.66, 0.49	.;P;P
Vest4		0.15
MutPred		0.38		Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);
MVP		0.54
MPC		0.38
ClinPred		0.50	T
GERP RS		2.3
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Varity_R		0.090
gMVP		0.075

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79679475;