8-42861868-G-GA

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_030954.4(RNF170):c.397-14_397-13insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000409 in 1,571,552 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (0 hom.)
• Consequence: RNF170 NM_030954.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.475

Genes affected

RNF170 (HGNC:25358): (ring finger protein 170) This gene encodes a RING domain-containing protein that resides in the endoplasmic reticulum (ER) membrane. This protein functions as an E3 ubiquitin ligase and mediates ubiquitination and processing of inositol 1,4,5-trisphosphate (IP3) receptors via the ER-associated protein degradation pathway. It is recruited to the activated IP3 receptors by the ERLIN1/ERLIN2 complex to which it is constitutively bound. Mutations in this gene are associated with autosomal dominant sensory ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP6: Variant 8-42861868-G-GA is Benign according to our data. Variant chr8-42861868-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 1284587.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF170	NM_030954.4	c.397-14_397-13insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000527424.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF170	ENST00000527424.6	c.397-14_397-13insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_030954.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000861 AC: 13 AN: 151000 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000886

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000444 AC: 630 AN: 1420440 Hom.: 0 Cov.: 28 AF XY: 0.000450 AC XY: 318 AN XY: 705934

Gnomad4 AFR exome AF: 0.000347

Gnomad4 AMR exome AF: 0.000947

Gnomad4 ASJ exome AF: 0.000601

Gnomad4 EAS exome AF: 0.000362

Gnomad4 SAS exome AF: 0.000826

Gnomad4 FIN exome AF: 0.000997

Gnomad4 NFE exome AF: 0.000383

Gnomad4 OTH exome AF: 0.000290

GnomAD4 genome AF: 0.0000860 AC: 13 AN: 151112 Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9 AN XY: 73732

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.0000659

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000886

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000793

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs558493564; hg19: chr8-42717011;