rs4834214

Variant names:

• chr4-127731072-G-A
• rs4834214
• NM_031291.4:c.232+295G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031291.4(SLC25A31):​c.232+295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,066 control chromosomes in the GnomAD database, including 28,014 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (28014 hom., cov: 32)
• Consequence: SLC25A31 NM_031291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A31	NM_031291.4	c.232+295G>A		intron_variant	Intron 1 of 5	ENST00000281154.6	NP_112581.1
SLC25A31	NM_001318467.2	c.232+295G>A		intron_variant	Intron 1 of 6		NP_001305396.1
SLC25A31	XM_011532298.3	c.232+295G>A		intron_variant	Intron 1 of 3		XP_011530600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A31	ENST00000281154.6	c.232+295G>A		intron_variant	Intron 1 of 5	1	NM_031291.4	ENSP00000281154.4

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91485 AN: 151948 Hom.: 27970 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.640

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.602 AC: 91580 AN: 152066 Hom.: 28014 Cov.: 32 AF XY: 0.601 AC XY: 44657 AN XY: 74308

African (AFR) AF: 0.685 AC: 28415 AN: 41478

American (AMR) AF: 0.629 AC: 9623 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2080 AN: 3468

East Asian (EAS) AF: 0.546 AC: 2817 AN: 5164

South Asian (SAS) AF: 0.695 AC: 3343 AN: 4808

European-Finnish (FIN) AF: 0.492 AC: 5199 AN: 10558

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38084 AN: 67984

Other (OTH) AF: 0.641 AC: 1352 AN: 2110

Alfa AF: 0.582 Hom.: 13664

Bravo AF: 0.614

Asia WGS AF: 0.645 AC: 2241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.22
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4834214; hg19: chr4-128652227;