rs3134269

Variant names:

• chr8-103409674-C-T
• rs3134269
• NM_030780.5:c.155-1890G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030780.5(SLC25A32):​c.155-1890G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 152,274 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.053 (272 hom., cov: 32)
• Consequence: SLC25A32 NM_030780.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 3 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: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ENSG00000285982 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A32	NM_030780.5	c.155-1890G>A		intron_variant	Intron 1 of 6	ENST00000297578.9	NP_110407.2
SLC25A32	NR_102337.2	n.325-1890G>A		intron_variant	Intron 1 of 5
SLC25A32	NR_102338.2	n.434-1890G>A		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A32	ENST00000297578.9	c.155-1890G>A		intron_variant	Intron 1 of 6	1	NM_030780.5	ENSP00000297578.4
ENSG00000285982	ENST00000649416.1	c.2-1890G>A		intron_variant	Intron 3 of 8			ENSP00000496817.1

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8067 AN: 152156 Hom.: 272 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0530 AC: 8066 AN: 152274 Hom.: 272 Cov.: 32 AF XY: 0.0511 AC XY: 3802 AN XY: 74462

African (AFR) AF: 0.0232 AC: 964 AN: 41552

American (AMR) AF: 0.0514 AC: 786 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3472

East Asian (EAS) AF: 0.00714 AC: 37 AN: 5184

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4828

European-Finnish (FIN) AF: 0.0484 AC: 514 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0782 AC: 5319 AN: 68020

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0681 Hom.: 182

Bravo AF: 0.0528

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.61
DANN	Benign	0.47
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs3134269; hg19: chr8-104421902;