17-81715021-C-T

Variant names:

• chr17-81715021-C-T
• rs3204270
• NM_012140.5:c.162C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012140.5(SLC25A10):​c.162C>T​(p.Thr54Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 1,609,912 control chromosomes in the GnomAD database, including 7,442 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.072 (535 hom., cov: 33)
  • Exomes 𝑓: 0.093 (6907 hom.)
• Consequence: SLC25A10 NM_012140.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.73
• Publications: 22 publications found

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]

SLC25A10 Gene-Disease associations (from GenCC):

• mitochondrial DNA depletion syndrome 19

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• mitochondrial disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000262660 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-3.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.099 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A10	NM_012140.5	c.162C>T	p.Thr54Thr	synonymous_variant	Exon 2 of 11	ENST00000350690.10	NP_036272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A10	ENST00000350690.10	c.162C>T	p.Thr54Thr	synonymous_variant	Exon 2 of 11	1	NM_012140.5	ENSP00000345580.5
ENSG00000262660	ENST00000571730.1	c.627C>T	p.Thr209Thr	synonymous_variant	Exon 6 of 15	2		ENSP00000461324.1

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10986 AN: 152218 Hom.: 534 Cov.: 33

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0703

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0942

GnomAD2 exomes AF: 0.0753 AC: 18398 AN: 244380 AF XY: 0.0766

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.0470

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.0923

GnomAD4 exome AF: 0.0931 AC: 135681 AN: 1457576 Hom.: 6907 Cov.: 32 AF XY: 0.0916 AC XY: 66408 AN XY: 725248

African (AFR) AF: 0.0158 AC: 529 AN: 33426

American (AMR) AF: 0.0505 AC: 2256 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3020 AN: 26110

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39690

South Asian (SAS) AF: 0.0392 AC: 3380 AN: 86180

European-Finnish (FIN) AF: 0.126 AC: 6395 AN: 50832

Middle Eastern (MID) AF: 0.102 AC: 474 AN: 4630

European-Non Finnish (NFE) AF: 0.103 AC: 114242 AN: 1111794

Other (OTH) AF: 0.0893 AC: 5380 AN: 60222

GnomAD4 genome AF: 0.0721 AC: 10982 AN: 152336 Hom.: 535 Cov.: 33 AF XY: 0.0712 AC XY: 5304 AN XY: 74496

African (AFR) AF: 0.0214 AC: 891 AN: 41592

American (AMR) AF: 0.0702 AC: 1074 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 404 AN: 3466

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4832

European-Finnish (FIN) AF: 0.118 AC: 1252 AN: 10622

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6872 AN: 68010

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.0879 Hom.: 452

Bravo AF: 0.0667

Asia WGS AF: 0.0150 AC: 51 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.1
DANN	Benign	0.68
PhyloP100		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs3204270; hg19: chr17-79682051; COSMIC: COSV58971344; COSMIC: COSV58971344;