chr17-8288435-GTCAA-G

Variant names:

• chr17-8288435-GTCAA-G
• rs138372313
• ENST00000579192.5:c.*43-7_*43-4delTTGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001320871.2(SLC25A35):​c.*43-7_*43-4delTTGA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 376,854 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (8 hom., cov: 31)
  • Exomes 𝑓: 0.0032 (3 hom.)
• Consequence: SLC25A35 NM_001320871.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0990

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-8288435-GTCAA-G is Benign according to our data. Variant chr17-8288435-GTCAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00666 (1011/151906) while in subpopulation AFR AF= 0.0186 (770/41420). AF 95% confidence interval is 0.0175. There are 8 homozygotes in gnomad4. There are 467 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RANGRF	NM_016492.5	c.-353_-350delTCAA		upstream_gene_variant		ENST00000226105.11	NP_057576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RANGRF	ENST00000226105.11	c.-353_-350delTCAA		upstream_gene_variant		1	NM_016492.5	ENSP00000226105.6

Frequencies

GnomAD3 genomes AF: 0.00663 AC: 1006 AN: 151786 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00374

Gnomad ASJ AF: 0.00376

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.00432

GnomAD4 exome AF: 0.00321 AC: 721 AN: 224948 Hom.: 3 AF XY: 0.00358 AC XY: 435 AN XY: 121398

Gnomad4 AFR exome AF: 0.0165

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.00322

Gnomad4 EAS exome AF: 0.00454

Gnomad4 SAS exome AF: 0.00833

Gnomad4 FIN exome AF: 0.000645

Gnomad4 NFE exome AF: 0.00126

Gnomad4 OTH exome AF: 0.00312

GnomAD4 genome AF: 0.00666 AC: 1011 AN: 151906 Hom.: 8 Cov.: 31 AF XY: 0.00629 AC XY: 467 AN XY: 74278

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.00374

Gnomad4 ASJ AF: 0.00376

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.00475

Bravo AF: 0.00731

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 04, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs138372313; hg19: chr17-8191753;