8-42865438-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_030954.4(RNF170):c.374G>A(p.Ser125Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,613,544 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 43 hom. )

Consequence

RNF170
NM_030954.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.83

Publications

7 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070908964).

BP6

Variant 8-42865438-C-T is Benign according to our data. Variant chr8-42865438-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 522306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030954.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF170	NM_030954.4	MANE Select	c.374G>A	p.Ser125Asn	missense	Exon 5 of 7	NP_112216.3
RNF170	NM_001160223.2		c.374G>A	p.Ser125Asn	missense	Exon 5 of 7	NP_001153695.1	Q96K19-1
RNF170	NM_001160224.2		c.374G>A	p.Ser125Asn	missense	Exon 5 of 6	NP_001153696.1	Q96K19-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF170	ENST00000527424.6	TSL:1 MANE Select	c.374G>A	p.Ser125Asn	missense	Exon 5 of 7	ENSP00000434797.1	Q96K19-1
RNF170	ENST00000534961.5	TSL:1	c.374G>A	p.Ser125Asn	missense	Exon 5 of 7	ENSP00000445725.1	Q96K19-1
RNF170	ENST00000319104.7	TSL:1	c.374G>A	p.Ser125Asn	missense	Exon 5 of 6	ENSP00000326138.3	Q96K19-3

Frequencies

GnomAD3 genomes

AF:

0.00368

AC:

559

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00858

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.00293

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00387

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.00476

AC:

1196

AN:

251134

AF XY:

0.00536

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.0163

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00457

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00384

AC:

5617

AN:

1461354

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

2968

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33468

American (AMR)

AF:

0.00338

AC:

151

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

375

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.00981

AC:

846

AN:

86236

European-Finnish (FIN)

AF:

0.00189

AC:

101

AN:

53366

Middle Eastern (MID)

AF:

0.0146

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00335

AC:

3723

AN:

1111640

Other (OTH)

AF:

0.00530

AC:

320

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

271

542

813

1084

1355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

134

268

402

536

670

<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:

0.00367

AC:

558

AN:

152190

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.000506

AC:

AN:

41542

American (AMR)

AF:

0.00857

AC:

131

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00995

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00293

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00387

AC:

263

AN:

67992

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00450

Hom.:

Bravo

AF:

0.00349

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00464

AC:

564

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00671

EpiControl

AF:

0.00676

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Autosomal dominant sensory ataxia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.14

Eigen

Benign

-0.091

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.022

MetaRNN

Benign

0.0071

MetaSVM

Benign

-0.46

MutationAssessor

Benign

0.91

PhyloP100

1.8

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.17

REVEL

Uncertain

0.32

Sift

Benign

0.41

Sift4G

Benign

0.56

Polyphen

0.068

Vest4

0.11

MVP

0.17

MPC

0.33

ClinPred

0.0097

GERP RS

5.4

Varity_R

0.078

gMVP

0.36

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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