rs139600871

Variant names:

• chr8-42861759-C-G
• rs139600871
• NM_030954.4:c.493G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-42861759-C-G
• chr8-42861759-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030954.4(RNF170):​c.493G>C​(p.Gly165Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,168 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF170 NM_030954.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58
• Publications: 0 publications found

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)

ENSG00000286837 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF170	NM_030954.4	MANE Select	c.493G>C	p.Gly165Arg	missense	Exon 6 of 7	NP_112216.3
	RNF170	NM_001160223.2		c.493G>C	p.Gly165Arg	missense	Exon 6 of 7	NP_001153695.1	Q96K19-1
	RNF170	NM_001160225.2		c.241G>C	p.Gly81Arg	missense	Exon 6 of 7	NP_001153697.1	Q96K19-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF170	ENST00000527424.6	TSL:1 MANE Select	c.493G>C	p.Gly165Arg	missense	Exon 6 of 7	ENSP00000434797.1	Q96K19-1
	RNF170	ENST00000534961.5	TSL:1	c.493G>C	p.Gly165Arg	missense	Exon 6 of 7	ENSP00000445725.1	Q96K19-1
	RNF170	ENST00000526349.5	TSL:1	c.241G>C	p.Gly81Arg	missense	Exon 6 of 7	ENSP00000435782.1	Q96K19-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460168 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726534

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110638

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal dominant sensory ataxia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-6.6	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.019	D
Polyphen		0.99	D
Vest4		0.71
MutPred		0.41		Gain of MoRF binding (P = 0.0086)
MVP		0.82
MPC		1.1
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.77
gMVP		0.95
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs139600871; hg19: chr8-42716902;