NM_031291.4:c.715C>T

Variant names:

• chr4-127768833-C-T
• rs766593441
• NM_031291.4:c.715C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_031291.4(SLC25A31):​c.715C>T​(p.Leu239Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000759 in 1,607,620 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000082 (2 hom.)
• Consequence: SLC25A31 NM_031291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.292
• Publications: 0 publications found

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]

LOC105377414 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.048865855).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031291.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A31	NM_031291.4	MANE Select	c.715C>T	p.Leu239Phe	missense	Exon 5 of 6	NP_112581.1	Q9H0C2
	SLC25A31	NM_001318467.2		c.715C>T	p.Leu239Phe	missense	Exon 5 of 7	NP_001305396.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A31	ENST00000281154.6	TSL:1 MANE Select	c.715C>T	p.Leu239Phe	missense	Exon 5 of 6	ENSP00000281154.4	Q9H0C2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000150 AC: 37 AN: 246854 AF XY: 0.000210

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000824 AC: 120 AN: 1455510 Hom.: 2 Cov.: 31 AF XY: 0.000123 AC XY: 89 AN XY: 723928

African (AFR) AF: 0.00 AC: 0 AN: 33270

American (AMR) AF: 0.00 AC: 0 AN: 43954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39318

South Asian (SAS) AF: 0.00133 AC: 113 AN: 84700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109370

Other (OTH) AF: 0.000116 AC: 7 AN: 60106

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74322

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000189 AC: 23

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.29
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.23
Sift	Uncertain	0.017	D
Sift4G	Benign	0.41	T
Polyphen		0.0060	B
Vest4		0.32
MutPred		0.33		Loss of catalytic residue at L239 (P = 0.1478)
MVP		0.38
MPC		0.76
ClinPred		0.092	T
GERP RS		2.7
Varity_R		0.13
gMVP		0.48
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs766593441; hg19: chr4-128689988;