Variant 12-98593667-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000188376.9(SLC25A3):c.-312G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 466,030 control chromosomes in the GnomAD database, including 1,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 263 hom., cov: 33)

Exomes 𝑓: 0.063 ( 903 hom. )

Consequence

SLC25A3
ENST00000188376.9 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.92

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 12-98593667-G-A is Benign according to our data. Variant chr12-98593667-G-A is described in ClinVar as [Benign]. Clinvar id is 310792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SLC25A3	NM_005888.4 link	c.-78G>A	upstream_gene_variant	ENST00000228318.8	NP_005879.1	Q00325-1A0A024RBH9Q6MZF9
SLC25A3	NM_002635.4 link	c.-78G>A	upstream_gene_variant	ENST00000552981.6	NP_002626.1	Q00325-2A0A024RBE8Q6MZF9
SLC25A3	NM_213611.3 link	c.-312G>A	upstream_gene_variant		NP_998776.1	Q00325-2A0A024RBE8Q6MZF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A3	ENST00000228318.8 link	c.-78G>A		upstream_gene_variant		5	NM_005888.4	ENSP00000228318.3		Q00325-1
SLC25A3	ENST00000552981.6 link	c.-78G>A		upstream_gene_variant		1	NM_002635.4	ENSP00000448708.2		Q00325-2

Frequencies

GnomAD3 genomes

AF:

0.0494

AC:

7521

AN:

152218

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.0593

Gnomad AMR

AF:

0.0391

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0431

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0526

Gnomad OTH

AF:

0.0439

GnomAD4 exome

AF:

0.0626

AC:

19628

AN:

313694

Hom.:

903

Cov.:

AF XY:

0.0651

AC XY:

10758

AN XY:

165266

show subpopulations

Gnomad4 AFR exome

AF:

0.0264

Gnomad4 AMR exome

AF:

0.0334

Gnomad4 ASJ exome

AF:

0.0502

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.0956

Gnomad4 FIN exome

AF:

0.0399

Gnomad4 NFE exome

AF:

0.0495

Gnomad4 OTH exome

AF:

0.0535

GnomAD4 genome

AF:

0.0494

AC:

7530

AN:

152336

Hom.:

263

Cov.:

AF XY:

0.0505

AC XY:

3764

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.0391

Gnomad4 ASJ

AF:

0.0461

Gnomad4 EAS

AF:

0.204

Gnomad4 SAS

AF:

0.0998

Gnomad4 FIN

AF:

0.0431

Gnomad4 NFE

AF:

0.0526

Gnomad4 OTH

AF:

0.0454

Alfa

AF:

0.0484

Hom.:

Bravo

AF:

0.0468

Asia WGS

AF:

0.132

AC:

457

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cardiomyopathy-hypotonia-lactic acidosis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

-0.77

CADD

Benign

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over