8-103404816-AC-GT

Variant names:

• chr8-103404816-AC-GT
• NM_030780.5:c.350_351delGTinsAC
• SLC25A32 p.Arg117His

Variant summary

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

The NM_030780.5(SLC25A32):​c.350_351delGTinsAC​(p.Arg117His) variant causes a missense 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R117C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A32 NM_030780.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 0 publications found

Genes affected

SLC25A32 (HGNC:29683): (solute carrier family 25 member 32) This gene encodes a member of the P(I/L)W subfamily of mitochondrial carrier family transport proteins. The encoded protein transports folate across the inner mitochondrial membrane. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2013]

SLC25A32 Gene-Disease associations (from GenCC):

• exercise intolerance, riboflavin-responsive

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ENSG00000285982 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030780.5. 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
	SLC25A32	NM_030780.5	MANE Select	c.350_351delGTinsAC	p.Arg117His	missense	N/A	NP_110407.2
	SLC25A32	NR_102338.2		n.629_630delGTinsAC		non_coding_transcript_exon	Exon 4 of 8
	SLC25A32	NR_102337.2		n.476-1493_476-1492delGTinsAC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A32	ENST00000297578.9	TSL:1 MANE Select	c.350_351delGTinsAC	p.Arg117His	missense	N/A	ENSP00000297578.4	Q9H2D1
	ENSG00000285982	ENST00000649416.1		c.197_198delGTinsAC	p.Arg66His	missense	N/A	ENSP00000496817.1	A0A3B3IRK5
	SLC25A32	ENST00000707124.1		c.419_420delGTinsAC	p.Arg140His	missense	N/A	ENSP00000516752.1	A0A9L9PY70

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.035

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: chr8-104417044;