chr17-81717813-CCT-TCC

Variant names:

• chr17-81717813-CCT-TCC
• NM_012140.5:c.657_659delCCTinsTCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_012140.5(SLC25A10):​c.657_659delCCTinsTCC​(p.Leu220Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P219P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A10 NM_012140.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.32
• Publications: 0 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, PanelApp Australia
• mitochondrial disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000262660 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A10	NM_012140.5	MANE Select	c.657_659delCCTinsTCC	p.Leu220Pro	missense	N/A	NP_036272.2
	SLC25A10	NM_001270953.2		c.574_576delCCTinsTCC	p.Pro192Ser	missense	N/A	NP_001257882.1	F6RGN5
	SLC25A10	NM_001270888.2		c.684_686delCCTinsTCC	p.Leu229Pro	missense	N/A	NP_001257817.1	Q9UBX3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A10	ENST00000350690.10	TSL:1 MANE Select	c.657_659delCCTinsTCC	p.Leu220Pro	missense	N/A	ENSP00000345580.5	Q9UBX3-1
	ENSG00000262660	ENST00000571730.1	TSL:2	c.1122_1124delCCTinsTCC	p.Leu375Pro	missense	N/A	ENSP00000461324.1	B4DLN1
	SLC25A10	ENST00000545862.5	TSL:1	c.574_576delCCTinsTCC	p.Pro192Ser	missense	N/A	ENSP00000446242.2	F6RGN5

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-79684843;