17-8288620-C-G

Variant names:

• chr17-8288620-C-G
• rs111476121
• ENST00000579192.5:c.*43-188G>C

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.*996G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000016 in 623,158 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: 0.0000016 (0 hom.)
• Consequence: SLC25A35 NM_201520.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 3 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=-0.71).

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.*996G>C		3_prime_UTR	Exon 6 of 6	NP_958928.1	Q3KQZ1-4
	SLC25A35	NM_001320871.2		c.*43-188G>C		intron	N/A	NP_001307800.1	Q3KQZ1-4
	SLC25A35	NR_135483.2		n.2541G>C		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.*43-188G>C		intron	N/A	ENSP00000462395.1	Q3KQZ1-4
	SLC25A35	ENST00000380067.6	TSL:2	c.*996G>C		3_prime_UTR	Exon 6 of 6	ENSP00000369407.2	Q3KQZ1-4
	SLC25A35	ENST00000581320.1	TSL:3	n.91-188G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000160 AC: 1 AN: 623158 Hom.: 0 Cov.: 8 AF XY: 0.00000302 AC XY: 1 AN XY: 331570

African (AFR) AF: 0.00 AC: 0 AN: 16226

American (AMR) AF: 0.00 AC: 0 AN: 30722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18826

East Asian (EAS) AF: 0.00 AC: 0 AN: 32280

South Asian (SAS) AF: 0.00 AC: 0 AN: 62164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3806

European-Non Finnish (NFE) AF: 0.00000254 AC: 1 AN: 392940

Other (OTH) AF: 0.00 AC: 0 AN: 32174

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		2.0
PromoterAI		-0.19	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: rs111476121; hg19: chr17-8191938;