8-42869991-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030954.4(RNF170):c.322+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 1,587,952 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (223 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (208 hom.)
• Consequence: RNF170 NM_030954.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.123

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-42869991-G-A is Benign according to our data. Variant chr8-42869991-G-A is described in ClinVar as [Benign]. Clinvar id is 1250481.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-42869991-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF170	NM_030954.4	c.322+13C>T		intron_variant		ENST00000527424.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF170	ENST00000527424.6	c.322+13C>T		intron_variant		1	NM_030954.4	P1

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4511 AN: 152078 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0292

GnomAD3 exomes AF: 0.00783 AC: 1963 AN: 250716 Hom.: 90 AF XY: 0.00585 AC XY: 793 AN XY: 135508

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00522

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000360

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000388

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00324 AC: 4648 AN: 1435756 Hom.: 208 Cov.: 28 AF XY: 0.00279 AC XY: 1999 AN XY: 715928

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.00594

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000758

Gnomad4 SAS exome AF: 0.000373

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000223

Gnomad4 OTH exome AF: 0.00763

GnomAD4 genome AF: 0.0298 AC: 4531 AN: 152196 Hom.: 223 Cov.: 32 AF XY: 0.0293 AC XY: 2180 AN XY: 74400

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0104

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0150 Hom.: 16

Bravo AF: 0.0344

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.8
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs58729340; hg19: chr8-42725134;