17-8288633-A-C

Variant names:

• chr17-8288633-A-C
• rs113617815
• ENST00000579192.5:c.*43-201T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_201520.3(SLC25A35):​c.*983T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 713,350 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC25A35 NM_201520.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 0 publications found

Genes affected

SLC25A35 (HGNC:31921): (solute carrier family 25 member 35) SLC25A35 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

RANGRF (HGNC:17679): (RAN guanine nucleotide release factor) This gene encodes a protein that has been shown to function as a guanine nucleotide release factor in mouse and to regulate the expression and function of the Nav1.5 cardiac sodium channel in human. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

RANGRF Gene-Disease associations (from GenCC):

• Brugada syndrome

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201520.3. 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
	SLC25A35	NM_201520.3		c.*983T>G		3_prime_UTR	Exon 6 of 6	NP_958928.1	Q3KQZ1-4
	SLC25A35	NM_001320871.2		c.*43-201T>G		intron	N/A	NP_001307800.1	Q3KQZ1-4
	SLC25A35	NR_135483.2		n.2528T>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A35	ENST00000579192.5	TSL:1	c.*43-201T>G		intron	N/A	ENSP00000462395.1	Q3KQZ1-4
	RANGRF	ENST00000939480.1		c.-156A>C		5_prime_UTR	Exon 1 of 5	ENSP00000609539.1
	SLC25A35	ENST00000380067.6	TSL:2	c.*983T>G		3_prime_UTR	Exon 6 of 6	ENSP00000369407.2	Q3KQZ1-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 1 AN: 713350 Hom.: 0 Cov.: 9 AF XY: 0.00000266 AC XY: 1 AN XY: 376394

African (AFR) AF: 0.00 AC: 0 AN: 18030

American (AMR) AF: 0.00 AC: 0 AN: 33472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20190

East Asian (EAS) AF: 0.00 AC: 0 AN: 32982

South Asian (SAS) AF: 0.0000150 AC: 1 AN: 66628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4224

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 466174

Other (OTH) AF: 0.00 AC: 0 AN: 35380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.45
PhyloP100		0.27
PromoterAI		-0.081	Neutral

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: rs113617815; hg19: chr17-8191951;