8-103404817-C-G

Variant names:

• chr8-103404817-C-G
• rs17803441
• NM_030780.5:c.350G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030780.5(SLC25A32):​c.350G>C​(p.Arg117Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027296335).

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.350G>C	p.Arg117Pro	missense	Exon 3 of 7	NP_110407.2
	SLC25A32	NR_102338.2		n.629G>C		non_coding_transcript_exon	Exon 4 of 8
	SLC25A32	NR_102337.2		n.476-1493G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A32	ENST00000297578.9	TSL:1 MANE Select	c.350G>C	p.Arg117Pro	missense	Exon 3 of 7	ENSP00000297578.4	Q9H2D1
	ENSG00000285982	ENST00000649416.1		c.197G>C	p.Arg66Pro	missense	Exon 5 of 9	ENSP00000496817.1	A0A3B3IRK5
	SLC25A32	ENST00000707124.1		c.419G>C	p.Arg140Pro	missense	Exon 3 of 7	ENSP00000516752.1	A0A9L9PY70

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.61	N
PhyloP100		-0.035
PrimateAI	Benign	0.29	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.15
Sift	Benign	0.40	T
Sift4G	Benign	0.34	T
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.26		Loss of solvent accessibility (P = 0.0703)
MVP		0.71
MPC		0.45
ClinPred		0.14	T
GERP RS		-2.2
Varity_R		0.088
gMVP		0.79
Mutation Taster		=83/17	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: rs17803441; hg19: chr8-104417045;