NM_001143780.3:c.*473G>A

Variant names:

• chr17-44319528-C-T
• rs12602832
• NM_001143780.3:c.*473G>A

Variant summary

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

The NM_001143780.3(SLC25A39):​c.*473G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 185,924 control chromosomes in the GnomAD database, including 655 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 0.072 (549 hom., cov: 32)
  • Exomes 𝑓: 0.067 (106 hom.)
• Consequence: SLC25A39 NM_001143780.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• Publications: 6 publications found

Genes affected

SLC25A39 (HGNC:24279): (solute carrier family 25 member 39) This gene encodes a member of the SLC25 transporter or mitochondrial carrier family of proteins. Members of this family are encoded by the nuclear genome while their protein products are usually embedded in the inner mitochondrial membrane and exhibit wide-ranging substrate specificity. Although the encoded protein is currently considered an orphan transporter, this protein is related to other carriers known to transport amino acids. This protein may play a role in iron homeostasis. [provided by RefSeq, Mar 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143780.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A39	NM_001143780.3	MANE Select	c.*473G>A		downstream_gene	N/A	NP_001137252.1
	SLC25A39	NM_001321241.2		c.*473G>A		downstream_gene	N/A	NP_001308170.1
	SLC25A39	NM_016016.4		c.*473G>A		downstream_gene	N/A	NP_057100.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A39	ENST00000377095.10	TSL:1 MANE Select	c.*473G>A		downstream_gene	N/A	ENSP00000366299.4
	SLC25A39	ENST00000225308.12	TSL:1	c.*473G>A		downstream_gene	N/A	ENSP00000225308.8
	SLC25A39	ENST00000590194.5	TSL:5	c.*473G>A		downstream_gene	N/A	ENSP00000467681.1

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10999 AN: 152154 Hom.: 549 Cov.: 32

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.0330

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.0817

GnomAD4 exome AF: 0.0667 AC: 2244 AN: 33652 Hom.: 106 AF XY: 0.0670 AC XY: 1182 AN XY: 17634

African (AFR) AF: 0.0142 AC: 11 AN: 774

American (AMR) AF: 0.0951 AC: 290 AN: 3048

Ashkenazi Jewish (ASJ) AF: 0.0368 AC: 21 AN: 570

East Asian (EAS) AF: 0.0304 AC: 54 AN: 1778

South Asian (SAS) AF: 0.0841 AC: 379 AN: 4506

European-Finnish (FIN) AF: 0.0883 AC: 103 AN: 1166

Middle Eastern (MID) AF: 0.0109 AC: 1 AN: 92

European-Non Finnish (NFE) AF: 0.0640 AC: 1280 AN: 20014

Other (OTH) AF: 0.0616 AC: 105 AN: 1704

GnomAD4 genome AF: 0.0722 AC: 10999 AN: 152272 Hom.: 549 Cov.: 32 AF XY: 0.0752 AC XY: 5596 AN XY: 74446

African (AFR) AF: 0.0191 AC: 795 AN: 41566

American (AMR) AF: 0.114 AC: 1738 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0496 AC: 172 AN: 3470

East Asian (EAS) AF: 0.0334 AC: 173 AN: 5176

South Asian (SAS) AF: 0.119 AC: 573 AN: 4828

European-Finnish (FIN) AF: 0.128 AC: 1354 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0881 AC: 5993 AN: 68018

Other (OTH) AF: 0.0799 AC: 169 AN: 2114

Alfa AF: 0.0756 Hom.: 706

Bravo AF: 0.0676

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.71
PhyloP100		-0.97

Splicing

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

Other links and lift over

dbSNP: rs12602832; hg19: chr17-42396896;