Genetic Variant SLC25A46:c.10+729T>G (chr5-110738976-T-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001303250.3(SLC25A46):c.10+729T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 1,454,162 control chromosomes in the GnomAD database, including 5,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.087 ( 600 hom., cov: 32)

Exomes 𝑓: 0.085 ( 4995 hom. )

Consequence

SLC25A46
NM_001303250.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0930

Publications

7 publications found

Variant links:

Genes affected

SLC25A46 (HGNC:25198): (solute carrier family 25 member 46) This gene encodes a mitochondrial solute carrier protein family member. It functions in promoting mitochondrial fission, and prevents the formation of hyperfilamentous mitochondria. Mutation of this gene results in neuropathy and optic atrophy. [provided by RefSeq, Aug 2016]

SLC25A46 links:

TMEM232 (HGNC:37270): (transmembrane protein 232) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM232 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 5-110738976-T-G is Benign according to our data. Variant chr5-110738976-T-G is described in ClinVar as [Benign]. Clinvar id is 1284005.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A46	NM_138773.4 link	c.-144T>G		upstream_gene_variant		ENST00000355943.8	NP_620128.1	Q96AG3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A46	ENST00000355943.8 link	c.-144T>G		upstream_gene_variant		1	NM_138773.4	ENSP00000348211.3		Q96AG3-1

Frequencies

GnomAD3 genomes

AF:

0.0867

AC:

13196

AN:

152192

Hom.:

598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0730

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.0812

Gnomad EAS

AF:

0.0248

Gnomad SAS

AF:

0.0366

Gnomad FIN

AF:

0.0921

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0935

Gnomad OTH

AF:

0.0861

GnomAD4 exome

AF:

0.0854

AC:

111135

AN:

1301852

Hom.:

4995

Cov.:

AF XY:

0.0841

AC XY:

53395

AN XY:

635028

show subpopulations

African (AFR)

AF:

0.0684

AC:

1942

AN:

28384

American (AMR)

AF:

0.126

AC:

2592

AN:

20534

Ashkenazi Jewish (ASJ)

AF:

0.0786

AC:

1572

AN:

19998

East Asian (EAS)

AF:

0.0234

AC:

817

AN:

34912

South Asian (SAS)

AF:

0.0364

AC:

2359

AN:

64850

European-Finnish (FIN)

AF:

0.0926

AC:

2957

AN:

31918

Middle Eastern (MID)

AF:

0.0758

AC:

281

AN:

3708

European-Non Finnish (NFE)

AF:

0.0902

AC:

94083

AN:

1043250

Other (OTH)

AF:

0.0835

AC:

4532

AN:

54298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

4874

9748

14622

19496

24370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0867

AC:

13211

AN:

152310

Hom.:

600

Cov.:

AF XY:

0.0872

AC XY:

6493

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0731

AC:

3039

AN:

41572

American (AMR)

AF:

0.126

AC:

1930

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0812

AC:

282

AN:

3472

East Asian (EAS)

AF:

0.0249

AC:

129

AN:

5188

South Asian (SAS)

AF:

0.0373

AC:

180

AN:

4832

European-Finnish (FIN)

AF:

0.0921

AC:

979

AN:

10624

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0935

AC:

6361

AN:

68004

Other (OTH)

AF:

0.0843

AC:

178

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

637

1275

1912

2550

3187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0760

Hom.:

237

Bravo

AF:

0.0913

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 14, 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

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.0

(source)

DANN

Benign

0.89

PhyloP100

0.093

PromoterAI

-0.32

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr5-110738976-T-G

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