dbSNP rs766593441: SLC25A31:p.Leu239Val (chr4-127768833-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031291.4(SLC25A31):c.715C>G(p.Leu239Val) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L239F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC25A31
NM_031291.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.292

Variant links:

Genes affected

SLC25A31 (HGNC:25319): (solute carrier family 25 member 31) The protein encoded by this gene is a member of the ADP/ATP carrier family of proteins that exchange cytosolic ADP for matrix ATP in the mitochondria. Cells over-expressing this gene have been shown to display an anti-apoptotic phenotype. This protein is also thought to play a role in spermatogenesis, where it is believed to associate with a part of the flagellar cytoskeleton and with glycolytic enzymes. Male mice with mutations in the mouse ortholog of this gene are sterile and spermatocytes display an early meiotic arrest phenotype. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

SLC25A31 links:

LOC105377414 (HGNC:):

LOC105377414 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051844597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A31	NM_031291.4 link	c.715C>G	p.Leu239Val	missense_variant	Exon 5 of 6	ENST00000281154.6	NP_112581.1	Q9H0C2
SLC25A31	NM_001318467.2 link	c.715C>G	p.Leu239Val	missense_variant	Exon 5 of 7		NP_001305396.1	Q9H0C2
SLC25A31	XM_011532298.3 link	c.442C>G	p.Leu148Val	missense_variant	Exon 3 of 4		XP_011530600.1
LOC105377414	XR_939188.3 link	n.565-5295G>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A31	ENST00000281154.6 link	c.715C>G	p.Leu239Val	missense_variant	Exon 5 of 6	1	NM_031291.4	ENSP00000281154.4		Q9H0C2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246854

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.099

DEOGEN2

Benign

0.11

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0052

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.67

PrimateAI

Benign

0.45

PROVEAN

Benign

0.65

REVEL

Benign

0.15

Sift

Benign

0.85

Sift4G

Benign

0.91

Polyphen

0.0020

Vest4

0.12

MutPred

0.22

Gain of helix (P = 0.2059);

MVP

0.19

MPC

0.33

ClinPred

0.052

GERP RS

2.7

Varity_R

0.057

gMVP

0.37

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over