3-66369505-CT-TC

Variant names:

• chr3-66369505-CT-TC
• NM_001379210.1:c.596_597delCTinsTC
• SLC25A26 p.Pro199Leu

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PS1

The NM_001379210.1(SLC25A26):​c.596_597delCTinsTC​(p.Pro199Leu) variant causes a missense change. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A26 NM_001379210.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.46
• Publications: 0 publications found

Genes affected

SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

SLC25A26 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• combined oxidative phosphorylation deficiency 28

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PS1: Transcript NM_001379210.1 (SLC25A26) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379210.1. 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
	SLC25A26	NM_001379210.1	MANE Select	c.596_597delCTinsTC	p.Pro199Leu	missense	N/A	NP_001366139.1	Q70HW3-1
	SLC25A26	NM_001400705.1		c.596_597delCTinsTC	p.Pro199Leu	missense	N/A	NP_001387634.1
	SLC25A26	NM_173471.4		c.596_597delCTinsTC	p.Pro199Leu	missense	N/A	NP_775742.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A26	ENST00000354883.11	TSL:2 MANE Select	c.596_597delCTinsTC	p.Pro199Leu	missense	N/A	ENSP00000346955.6	Q70HW3-1
	SLC25A26	ENST00000336733.10	TSL:1	c.332_333delCTinsTC	p.Pro111Leu	missense	N/A	ENSP00000336801.5	Q70HW3-2
	SLC25A26	ENST00000464350.6	TSL:1	n.*125_*126delCTinsTC		non_coding_transcript_exon	Exon 8 of 13	ENSP00000432574.2	H0YCZ5

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		6.5

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: chr3-66419929;