8-103404817-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030780.5(SLC25A32):​c.350G>A​(p.Arg117His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,611,668 control chromosomes in the GnomAD database, including 4,020 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.052 (269 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3751 hom.)
• Consequence: SLC25A32 NM_030780.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0350

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]

ENSG00000285982 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013113916).
• BP6: Variant 8-103404817-C-T is Benign according to our data. Variant chr8-103404817-C-T is described in ClinVar as [Benign]. Clinvar id is 1280576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A32	NM_030780.5	c.350G>A	p.Arg117His	missense_variant	Exon 3 of 7	ENST00000297578.9	NP_110407.2
SLC25A32	NR_102338.2	n.629G>A		non_coding_transcript_exon_variant	Exon 4 of 8
SLC25A32	NR_102337.2	n.476-1493G>A		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A32	ENST00000297578.9	c.350G>A	p.Arg117His	missense_variant	Exon 3 of 7	1	NM_030780.5	ENSP00000297578.4
ENSG00000285982	ENST00000649416.1	c.197G>A	p.Arg66His	missense_variant	Exon 5 of 9			ENSP00000496817.1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7892 AN: 152158 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.0656

GnomAD3 exomes AF: 0.0491 AC: 12307 AN: 250888 Hom.: 399 AF XY: 0.0489 AC XY: 6633 AN XY: 135630

Gnomad AFR exome AF: 0.0186

Gnomad AMR exome AF: 0.0339

Gnomad ASJ exome AF: 0.0555

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0180

Gnomad FIN exome AF: 0.0482

Gnomad NFE exome AF: 0.0734

Gnomad OTH exome AF: 0.0587

GnomAD4 exome AF: 0.0678 AC: 99009 AN: 1459392 Hom.: 3751 Cov.: 29 AF XY: 0.0663 AC XY: 48131 AN XY: 726194

Gnomad4 AFR exome AF: 0.0155

Gnomad4 AMR exome AF: 0.0362

Gnomad4 ASJ exome AF: 0.0535

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0182

Gnomad4 FIN exome AF: 0.0484

Gnomad4 NFE exome AF: 0.0788

Gnomad4 OTH exome AF: 0.0607

GnomAD4 genome AF: 0.0518 AC: 7892 AN: 152276 Hom.: 269 Cov.: 32 AF XY: 0.0498 AC XY: 3711 AN XY: 74468

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.0481

Gnomad4 NFE AF: 0.0782

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0700 Hom.: 837

Bravo AF: 0.0514

TwinsUK AF: 0.0793 AC: 294

ALSPAC AF: 0.0789 AC: 304

ESP6500AA AF: 0.0241 AC: 106

ESP6500EA AF: 0.0786 AC: 676

ExAC AF: 0.0477 AC: 5788

Asia WGS AF: 0.00837 AC: 29 AN: 3478

EpiCase AF: 0.0762

EpiControl AF: 0.0746

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jul 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.072	T;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.040	N
LIST_S2	Uncertain	0.91	D;D
MetaRNN	Benign	0.0013	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.64	N;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.15
Sift	Benign	0.099	T;.
Sift4G	Benign	0.14	T;.
Polyphen		0.074	B;.
Vest4		0.043
MPC		0.69
ClinPred		0.016	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.027
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs17803441; hg19: chr8-104417045;