chr4-127730191-C-G

Variant names:

• chr4-127730191-C-G
• rs2279070
• NM_031291.4:c.-355C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031291.4(SLC25A31):​c.-355C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,190 control chromosomes in the GnomAD database, including 29,476 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 0.62 (29476 hom., cov: 33)
• Consequence: SLC25A31 NM_031291.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.40

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A31	NM_031291.4	c.-355C>G		upstream_gene_variant		ENST00000281154.6	NP_112581.1
SLC25A31	NM_001318467.2	c.-355C>G		upstream_gene_variant			NP_001305396.1
SLC25A31	XM_011532298.3	c.-355C>G		upstream_gene_variant			XP_011530600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A31	ENST00000281154.6	c.-355C>G		upstream_gene_variant		1	NM_031291.4	ENSP00000281154.4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93633 AN: 152072 Hom.: 29436 Cov.: 33

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.616 AC: 93726 AN: 152190 Hom.: 29476 Cov.: 33 AF XY: 0.614 AC XY: 45674 AN XY: 74404

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.650

Alfa AF: 0.581 Hom.: 3251

Bravo AF: 0.630

Asia WGS AF: 0.645 AC: 2242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.014
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2279070; hg19: chr4-128651346;