4-127730693-G-T

Position:

• chr4-127730693-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031291.4(SLC25A31):​c.148G>T​(p.Val50Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A31 NM_031291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A31	NM_031291.4	c.148G>T	p.Val50Leu	missense_variant	1/6	ENST00000281154.6	NP_112581.1
SLC25A31	NM_001318467.2	c.148G>T	p.Val50Leu	missense_variant	1/7		NP_001305396.1
SLC25A31	XM_011532298.3	c.148G>T	p.Val50Leu	missense_variant	1/4		XP_011530600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A31	ENST00000281154.6	c.148G>T	p.Val50Leu	missense_variant	1/6	1	NM_031291.4	ENSP00000281154.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2024

The c.148G>T (p.V50L) alteration is located in exon 1 (coding exon 1) of the SLC25A31 gene. This alteration results from a G to T substitution at nucleotide position 148, causing the valine (V) at amino acid position 50 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.89	L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.49
Sift	Benign	0.16	T
Sift4G	Benign	0.30	T
Polyphen		0.042	B
Vest4		0.51
MutPred		0.73		Loss of sheet (P = 0.007);
MVP		0.65
MPC		0.69
ClinPred		0.62	D
GERP RS		3.8
Varity_R		0.21
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs894910174; hg19: chr4-128651848;