rs73634689

Variant names:

• chr8-42850871-C-A
• ENST00000319104.7:c.523G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-42850871-C-A
• chr8-42850871-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001160224.2(RNF170):​c.523G>T​(p.Asp175Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D175N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RNF170 NM_001160224.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082799375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF170	NM_001160224.2	c.523G>T	p.Asp175Tyr	missense_variant	Exon 6 of 6		NP_001153696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF170	ENST00000319104.7	c.523G>T	p.Asp175Tyr	missense_variant	Exon 6 of 6	1		ENSP00000326138.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399396 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.81
DANN	Benign	0.63
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.75	T
PROVEAN	Benign	3.8	N
REVEL	Benign	0.14
Sift	Benign	0.14	T
Sift4G	Benign	0.36	T
Polyphen		0.55	P
Vest4		0.12
MutPred		0.43		Loss of disorder (P = 0.0259);
MVP		0.12
ClinPred		0.079	T
GERP RS		0.11

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-42706014;