dbSNP rs778865084: SLC25A3:p.Phe2Leu (chr12-98593984-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002635.4(SLC25A3):c.6C>A(p.Phe2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

SLC25A3
NM_002635.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
mitochondrial disease
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

SLC25A3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3570938).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002635.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A3	NM_005888.4	MANE Plus Clinical	c.6C>A	p.Phe2Leu	missense	Exon 2 of 8	NP_005879.1	Q00325-1
SLC25A3	NM_002635.4	MANE Select	c.6C>A	p.Phe2Leu	missense	Exon 2 of 8	NP_002626.1	A0A024RBE8
SLC25A3	NM_213611.3		c.6C>A	p.Phe2Leu	missense	Exon 1 of 7	NP_998776.1	Q00325-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A3	ENST00000228318.8	TSL:5 MANE Plus Clinical	c.6C>A	p.Phe2Leu	missense	Exon 2 of 8	ENSP00000228318.3	Q00325-1
SLC25A3	ENST00000552981.6	TSL:1 MANE Select	c.6C>A	p.Phe2Leu	missense	Exon 2 of 8	ENSP00000448708.2	Q00325-2
SLC25A3	ENST00000188376.9	TSL:1	c.6C>A	p.Phe2Leu	missense	Exon 1 of 7	ENSP00000188376.5	Q00325-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.076

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.84

M_CAP

Benign

0.081

MetaRNN

Benign

0.36

MetaSVM

Uncertain

-0.065

MutationAssessor

Benign

0.55

PhyloP100

1.8

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.33

Sift

Benign

0.076

Sift4G

Benign

0.086

Polyphen

0.0010

Vest4

0.48

MutPred

0.20

Gain of disorder (P = 0.111)

MVP

0.90

MPC

0.51

ClinPred

0.62

GERP RS

3.7

PromoterAI

-0.055

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.77

Mutation Taster

=60/40

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over