rs4834214

Positions:

• chr4-127731072-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC25A31	NM_031291.4	c.232+295G>A		intron_variant		ENST00000281154.6	NP_112581.1
SLC25A31	NM_001318467.2	c.232+295G>A		intron_variant			NP_001305396.1
SLC25A31	XM_011532298.3	c.232+295G>A		intron_variant			XP_011530600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A31	ENST00000281154.6	c.232+295G>A		intron_variant		1	NM_031291.4	ENSP00000281154	P1

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

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.641

Alfa AF: 0.584 Hom.: 12429

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

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

Other links and lift over

dbSNP: rs4834214; hg19: chr4-128652227;