17-75273595-CAG-TAA

Variant names:

• chr17-75273595-CAG-TAA
• NM_001126121.2:c.817_819delCTGinsTTA
• SLC25A19 p.274

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_001126121.2(SLC25A19):​c.817_819delCTGinsTTA​(p.274) variant causes a synonymous change involving the alteration of a non-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. L273L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A19 NM_001126121.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 0 publications found

Genes affected

SLC25A19 (HGNC:14409): (solute carrier family 25 member 19) This gene encodes a mitochondrial protein that is a member of the solute carrier family. Although this protein was initially thought to be the mitochondrial deoxynucleotide carrier involved in the uptake of deoxynucleotides into the matrix of the mitochondria, further studies have demonstrated that this protein instead functions as the mitochondrial thiamine pyrophosphate carrier, which transports thiamine pyrophosphates into mitochondria. Mutations in this gene cause microcephaly, Amish type, a metabolic disease that results in severe congenital microcephaly, severe 2-ketoglutaric aciduria, and death within the first year. Multiple alternatively spliced variants, encoding the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

MIF4GD-DT (HGNC:55335): (MIF4GD divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=2.1 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126121.2. 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
	SLC25A19	NM_001126121.2	MANE Select	c.817_819delCTGinsTTA	p.274	synonymous	N/A	NP_001119593.1	Q9HC21-1
	SLC25A19	NM_001126122.2		c.817_819delCTGinsTTA	p.274	synonymous	N/A	NP_001119594.1	Q9HC21-1
	SLC25A19	NM_021734.5		c.817_819delCTGinsTTA	p.274	synonymous	N/A	NP_068380.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A19	ENST00000416858.7	TSL:1 MANE Select	c.817_819delCTGinsTTA	p.274	synonymous	N/A	ENSP00000397818.2	Q9HC21-1
	SLC25A19	ENST00000402418.7	TSL:1	c.817_819delCTGinsTTA	p.274	synonymous	N/A	ENSP00000385312.3	Q9HC21-1
	SLC25A19	ENST00000320362.7	TSL:2	c.817_819delCTGinsTTA	p.274	synonymous	N/A	ENSP00000319574.3	Q9HC21-1

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		2.1

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: chr17-73269676;