8-103404817-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). 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: 𝑓 0.052 ( 269 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3751 hom. )

Consequence

SLC25A32
NM_030780.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0350

Publications

26 publications found

Variant links:

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

SLC25A32 links:

ENSG00000285982 (HGNC:):

ENSG00000285982 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 CliVar as Benign. Clinvar id is 1280576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-103404817-C-T is described in CliVar as Benign. Clinvar id is 1280576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-103404817-C-T is described in CliVar as Benign. Clinvar id is 1280576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-103404817-C-T is described in CliVar 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 link	c.350G>A	p.Arg117His	missense_variant	Exon 3 of 7	ENST00000297578.9	NP_110407.2	Q9H2D1
SLC25A32	NR_102338.2 link	n.629G>A		non_coding_transcript_exon_variant	Exon 4 of 8
SLC25A32	NR_102337.2 link	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 link	c.350G>A	p.Arg117His	missense_variant	Exon 3 of 7	1	NM_030780.5	ENSP00000297578.4		Q9H2D1
ENSG00000285982	ENST00000649416.1 link	c.197G>A	p.Arg66His	missense_variant	Exon 5 of 9			ENSP00000496817.1		A0A3B3IRK5

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7892

AN:

152158

Hom.:

269

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0491

AC:

12307

AN:

250888

AF XY:

0.0489

show subpopulations

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 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.:

AF XY:

0.0663

AC XY:

48131

AN XY:

726194

show subpopulations

African (AFR)

AF:

0.0155

AC:

518

AN:

33464

American (AMR)

AF:

0.0362

AC:

1617

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.0535

AC:

1397

AN:

26110

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39670

South Asian (SAS)

AF:

0.0182

AC:

1572

AN:

86190

European-Finnish (FIN)

AF:

0.0484

AC:

2578

AN:

53300

Middle Eastern (MID)

AF:

0.0342

AC:

197

AN:

5762

European-Non Finnish (NFE)

AF:

0.0788

AC:

87468

AN:

1109916

Other (OTH)

AF:

0.0607

AC:

3659

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

4080

8160

12239

16319

20399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3178

6356

9534

12712

15890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0518

AC:

7892

AN:

152276

Hom.:

269

Cov.:

AF XY:

0.0498

AC XY:

3711

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0200

AC:

833

AN:

41566

American (AMR)

AF:

0.0512

AC:

783

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0525

AC:

182

AN:

3468

East Asian (EAS)

AF:

0.000578

AC:

AN:

5188

South Asian (SAS)

AF:

0.0149

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0481

AC:

510

AN:

10602

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0782

AC:

5319

AN:

68002

Other (OTH)

AF:

0.0653

AC:

138

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

375

751

1126

1502

1877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0667

Hom.:

1097

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:

AN:

3478

EpiCase

AF:

0.0762

EpiControl

AF:

0.0746

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.072

T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.040

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.64

N;.

PhyloP100

-0.035

PrimateAI

Benign

0.29

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

GERP RS

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.41

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over