rs200706742

Variant names:

• chr17-81719939-G-A
• rs200706742
• NM_012140.5:c.763-37G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-81719939-G-A
• chr17-81719939-G-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_012140.5(SLC25A10):​c.763-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000648 in 1,613,572 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00065 (8 hom.)
• Consequence: SLC25A10 NM_012140.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.143
• Publications: 1 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-81719939-G-A is Benign according to our data. Variant chr17-81719939-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012140.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A10	NM_012140.5	MANE Select	c.763-37G>A		intron	N/A	NP_036272.2
	SLC25A10	NM_001270953.2		c.680-37G>A		intron	N/A	NP_001257882.1
	SLC25A10	NM_001270888.2		c.790-37G>A		intron	N/A	NP_001257817.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A10	ENST00000350690.10	TSL:1 MANE Select	c.763-37G>A		intron	N/A	ENSP00000345580.5
	ENSG00000262660	ENST00000571730.1	TSL:2	c.1228-37G>A		intron	N/A	ENSP00000461324.1
	SLC25A10	ENST00000545862.5	TSL:1	c.680-37G>A		intron	N/A	ENSP00000446242.2

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152192 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00114 AC: 285 AN: 250898 AF XY: 0.00118

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000838

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.000651 AC: 952 AN: 1461264 Hom.: 8 Cov.: 31 AF XY: 0.000681 AC XY: 495 AN XY: 726938

African (AFR) AF: 0.00105 AC: 35 AN: 33480

American (AMR) AF: 0.00206 AC: 92 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00197 AC: 170 AN: 86256

European-Finnish (FIN) AF: 0.000170 AC: 9 AN: 52834

Middle Eastern (MID) AF: 0.00938 AC: 54 AN: 5758

European-Non Finnish (NFE) AF: 0.000412 AC: 458 AN: 1111994

Other (OTH) AF: 0.00144 AC: 87 AN: 60386

GnomAD4 genome AF: 0.000611 AC: 93 AN: 152308 Hom.: 0 Cov.: 34 AF XY: 0.000591 AC XY: 44 AN XY: 74468

African (AFR) AF: 0.000361 AC: 15 AN: 41574

American (AMR) AF: 0.00137 AC: 21 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.000733

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Mitochondrial DNA depletion syndrome 19 (1)
-	-	1	not provided (1)
-	-	1	SLC25A10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.52
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism

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: rs200706742; hg19: chr17-79686969;