rs11544648

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005888.4(SLC25A3):c.439T>C(p.Leu147Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,613,580 control chromosomes in the GnomAD database, including 428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 210 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 218 hom. )

Consequence

SLC25A3
NM_005888.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.210

Publications

2 publications found

Variant links:

Genes affected

SLC25A3 (HGNC:10989): (solute carrier family 25 member 3) The protein encoded by this gene catalyzes the transport of phosphate into the mitochondrial matrix, either by proton cotransport or in exchange for hydroxyl ions. The protein contains three related segments arranged in tandem which are related to those found in other characterized members of the mitochondrial carrier family. Both the N-terminal and C-terminal regions of this protein protrude toward the cytosol. Multiple alternatively spliced transcript variants have been isolated. [provided by RefSeq, Jul 2008]

SLC25A3 Gene-Disease associations (from GenCC):

cardiomyopathy-hypotonia-lactic acidosis syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
mitochondrial disease
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

SLC25A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 12-98598012-T-C is Benign according to our data. Variant chr12-98598012-T-C is described in ClinVar as [Benign]. Clinvar id is 139148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A3	NM_005888.4 link	c.439T>C	p.Leu147Leu	synonymous_variant	Exon 4 of 8	ENST00000228318.8	NP_005879.1	Q00325-1A0A024RBH9Q6MZF9
SLC25A3	NM_002635.4 link	c.436T>C	p.Leu146Leu	synonymous_variant	Exon 4 of 8	ENST00000552981.6	NP_002626.1	Q00325-2A0A024RBE8Q6MZF9
SLC25A3	NM_213611.3 link	c.436T>C	p.Leu146Leu	synonymous_variant	Exon 3 of 7		NP_998776.1	Q00325-2A0A024RBE8Q6MZF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A3	ENST00000228318.8 link	c.439T>C	p.Leu147Leu	synonymous_variant	Exon 4 of 8	5	NM_005888.4	ENSP00000228318.3		Q00325-1
SLC25A3	ENST00000552981.6 link	c.436T>C	p.Leu146Leu	synonymous_variant	Exon 4 of 8	1	NM_002635.4	ENSP00000448708.2		Q00325-2

Frequencies

GnomAD3 genomes

AF:

0.0292

AC:

4450

AN:

152142

Hom.:

210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0993

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.0192

GnomAD2 exomes

AF:

0.00837

AC:

2104

AN:

251478

AF XY:

0.00628

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.00520

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000756

Gnomad OTH exome

AF:

0.00635

GnomAD4 exome

AF:

0.00351

AC:

5134

AN:

1461320

Hom.:

218

Cov.:

AF XY:

0.00314

AC XY:

2286

AN XY:

726998

show subpopulations

African (AFR)

AF:

0.104

AC:

3463

AN:

33448

American (AMR)

AF:

0.00691

AC:

309

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00976

AC:

255

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000209

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000553

AC:

615

AN:

1111518

Other (OTH)

AF:

0.00742

AC:

448

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

247

494

741

988

1235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0293

AC:

4454

AN:

152260

Hom.:

210

Cov.:

AF XY:

0.0280

AC XY:

2082

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0991

AC:

4117

AN:

41542

American (AMR)

AF:

0.0124

AC:

190

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000956

AC:

AN:

68024

Other (OTH)

AF:

0.0190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

200

400

600

800

1000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.0337

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 15, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 06, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Cardiomyopathy-hypotonia-lactic acidosis syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.2

(source)

DANN

Benign

0.63

PhyloP100

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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rs11544648

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