Variant rs73634689 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001160224.2(RNF170):c.523G>A(p.Asp175Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,551,614 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.010 ( 27 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 25 hom. )

Consequence

RNF170
NM_001160224.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.0540

Variant links:

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]

RNF170 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004593134).

BP6

Variant 8-42850871-C-T is Benign according to our data. Variant chr8-42850871-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1284768.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-42850871-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1583/152212) while in subpopulation AFR AF= 0.0314 (1305/41512). AF 95% confidence interval is 0.03. There are 27 homozygotes in gnomad4. There are 713 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF170	NM_001160224.2 link	c.523G>A	p.Asp175Asn	missense_variant	Exon 6 of 6		NP_001153696.1	Q96K19-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF170	ENST00000319104.7 link	c.523G>A	p.Asp175Asn	missense_variant	Exon 6 of 6	1		ENSP00000326138.3		Q96K19-3

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1585

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.00404

AC:

622

AN:

154128

Hom.:

AF XY:

0.00351

AC XY:

287

AN XY:

81872

show subpopulations

Gnomad AFR exome

AF:

0.0305

Gnomad AMR exome

AF:

0.00559

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.0000594

Gnomad NFE exome

AF:

0.00143

Gnomad OTH exome

AF:

0.00616

GnomAD4 exome

AF:

0.00222

AC:

3112

AN:

1399402

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1430

AN XY:

690202

show subpopulations

Gnomad4 AFR exome

AF:

0.0327

Gnomad4 AMR exome

AF:

0.00591

Gnomad4 ASJ exome

AF:

0.0140

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000757

Gnomad4 FIN exome

AF:

0.0000609

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.00491

GnomAD4 genome

AF:

0.0104

AC:

1583

AN:

152212

Hom.:

Cov.:

AF XY:

0.00958

AC XY:

713

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0314

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00366

Hom.:

Bravo

AF:

0.0115

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.0246

AC:

ESP6500EA

AF:

0.00157

AC:

ExAC

AF:

0.00396

AC:

101

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.0

DANN

Benign

0.95

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.80

PROVEAN

Benign

1.7

REVEL

Benign

0.079

Sift

Benign

0.44

Sift4G

Benign

0.86

Polyphen

0.023

Vest4

0.10

MVP

0.20

ClinPred

0.00024

GERP RS

0.11

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over