ENST00000319104.7:c.523G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000319104.7(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. 13/16 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
ENST00000319104.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.0540

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant sensory ataxia 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
spastic paraplegia 85, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

RNF170 links:

ENSG00000286837 (HGNC:):

ENSG00000286837 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1284768.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0104 (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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000319104.7. 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
	RNF170	NM_001160224.2		c.523G>A	p.Asp175Asn	missense	Exon 6 of 6	NP_001153696.1	Q96K19-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF170	ENST00000319104.7	TSL:1	c.523G>A	p.Asp175Asn	missense	Exon 6 of 6	ENSP00000326138.3	Q96K19-3
	ENSG00000286837	ENST00000797430.1		n.532+6999C>T		intron	N/A

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

GnomAD2 exomes

AF:

0.00404

AC:

622

AN:

154128

AF XY:

0.00351

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 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

African (AFR)

AF:

0.0327

AC:

1033

AN:

31598

American (AMR)

AF:

0.00591

AC:

211

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.0140

AC:

352

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000757

AC:

AN:

79224

European-Finnish (FIN)

AF:

0.0000609

AC:

AN:

49278

Middle Eastern (MID)

AF:

0.0100

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00108

AC:

1165

AN:

1078976

Other (OTH)

AF:

0.00491

AC:

285

AN:

58004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

195

390

584

779

974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0104

AC:

1583

AN:

152212

Hom.:

Cov.:

AF XY:

0.00958

AC XY:

713

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0314

AC:

1305

AN:

41512

American (AMR)

AF:

0.00667

AC:

102

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00134

AC:

AN:

68014

Other (OTH)

AF:

0.0118

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

135

203

270

338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00534

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.0

(source)

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

PhyloP100

0.054

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

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over