chr17-8288633-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_201520.3(SLC25A35):​c.*983T>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 0.0224 in 865,558 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (139 hom., cov: 32)
  • Exomes 𝑓: 0.020 (213 hom.)
• Consequence: SLC25A35 NM_201520.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.269
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-8288633-A-G is Benign according to our data. Variant chr17-8288633-A-G is described in ClinVar as Benign. ClinVar VariationId is 1292115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0677 is higher than 0.05.

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>C		3_prime_UTR	Exon 6 of 6	NP_958928.1	Q3KQZ1-4
	SLC25A35	NM_001320871.2		c.*43-201T>C		intron	N/A	NP_001307800.1	Q3KQZ1-4
	SLC25A35	NR_135483.2		n.2528T>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.*43-201T>C		intron	N/A	ENSP00000462395.1	Q3KQZ1-4
	RANGRF	ENST00000939480.1		c.-156A>G		5_prime_UTR	Exon 1 of 5	ENSP00000609539.1
	SLC25A35	ENST00000380067.6	TSL:2	c.*983T>C		3_prime_UTR	Exon 6 of 6	ENSP00000369407.2	Q3KQZ1-4

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5063 AN: 152184 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0241

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0364

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.0200 AC: 14255 AN: 713256 Hom.: 213 Cov.: 9 AF XY: 0.0204 AC XY: 7681 AN XY: 376354

African (AFR) AF: 0.0704 AC: 1268 AN: 18022

American (AMR) AF: 0.0150 AC: 501 AN: 33472

Ashkenazi Jewish (ASJ) AF: 0.0119 AC: 241 AN: 20190

East Asian (EAS) AF: 0.00133 AC: 44 AN: 32982

South Asian (SAS) AF: 0.0359 AC: 2390 AN: 66624

European-Finnish (FIN) AF: 0.0209 AC: 758 AN: 36268

Middle Eastern (MID) AF: 0.0471 AC: 199 AN: 4224

European-Non Finnish (NFE) AF: 0.0172 AC: 8024 AN: 466096

Other (OTH) AF: 0.0235 AC: 830 AN: 35378

GnomAD4 genome AF: 0.0335 AC: 5101 AN: 152302 Hom.: 139 Cov.: 32 AF XY: 0.0336 AC XY: 2505 AN XY: 74482

African (AFR) AF: 0.0698 AC: 2901 AN: 41562

American (AMR) AF: 0.0240 AC: 367 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.00348 AC: 18 AN: 5172

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4826

European-Finnish (FIN) AF: 0.0250 AC: 265 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0186 AC: 1268 AN: 68028

Other (OTH) AF: 0.0232 AC: 49 AN: 2116

Alfa AF: 0.0264 Hom.: 31

Bravo AF: 0.0346

Asia WGS AF: 0.0560 AC: 193 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.1
DANN	Benign	0.52
PhyloP100		0.27
PromoterAI		-0.043	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV56839640; COSMIC: COSV56839640;