dbSNP rs846111: RNF207:p.Gly603Asp (chr1-6219310-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207396.3(RNF207):c.1808G>A(p.Gly603Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. G603A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RNF207
NM_207396.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.117

Variant links:

Genes affected

RNF207 (HGNC:32947): (ring finger protein 207) Enables Hsp70 protein binding activity; chaperone binding activity; and transmembrane transporter binding activity. Involved in positive regulation of delayed rectifier potassium channel activity; positive regulation of gene expression; and positive regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RNF207 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040579766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF207	NM_207396.3 link	c.1808G>A	p.Gly603Asp	missense_variant	Exon 18 of 18	ENST00000377939.5	NP_997279.2	Q6ZRF8-1
RNF207	XM_047420021.1 link	c.1874G>A	p.Gly625Asp	missense_variant	Exon 17 of 17		XP_047275977.1
RNF207	XM_047420010.1 link	c.1469G>A	p.Gly490Asp	missense_variant	Exon 17 of 17		XP_047275966.1
RNF207	XM_011541439.4 link	c.1403G>A	p.Gly468Asp	missense_variant	Exon 17 of 17		XP_011539741.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF207	ENST00000377939.5 link	c.1808G>A	p.Gly603Asp	missense_variant	Exon 18 of 18	5	NM_207396.3	ENSP00000367173.4	Q6ZRF8-1
RNF207	ENST00000483336.1 link	n.440G>A		non_coding_transcript_exon_variant	Exon 4 of 4	3
RNF207	ENST00000496676.5 link	n.1525G>A		non_coding_transcript_exon_variant	Exon 10 of 10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726900

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.2

DANN

Benign

0.61

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.37

M_CAP

Benign

0.0050

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.24

PROVEAN

Benign

0.37

REVEL

Benign

0.065

Sift

Benign

0.43

Sift4G

Benign

0.65

Polyphen

0.019

Vest4

0.11

MutPred

0.071

Gain of solvent accessibility (P = 0.1045);

MVP

0.13

MPC

0.22

ClinPred

0.041

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.082

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over