Genetic Variant RNF207:p.Gly603Ala (chr1-6219310-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_207396.3(RNF207):c.1808G>C(p.Gly603Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,612,148 control chromosomes in the GnomAD database, including 55,343 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3819 hom., cov: 31)

Exomes 𝑓: 0.26 ( 51524 hom. )

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044692755).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF207	NM_207396.3 link	c.1808G>C	p.Gly603Ala	missense_variant	Exon 18 of 18	ENST00000377939.5	NP_997279.2	Q6ZRF8-1
RNF207	XM_047420021.1 link	c.1874G>C	p.Gly625Ala	missense_variant	Exon 17 of 17		XP_047275977.1
RNF207	XM_047420010.1 link	c.1469G>C	p.Gly490Ala	missense_variant	Exon 17 of 17		XP_047275966.1
RNF207	XM_011541439.4 link	c.1403G>C	p.Gly468Ala	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>C	p.Gly603Ala	missense_variant	Exon 18 of 18	5	NM_207396.3	ENSP00000367173.4	Q6ZRF8-1
RNF207	ENST00000483336.1 link	n.440G>C		non_coding_transcript_exon_variant	Exon 4 of 4	3
RNF207	ENST00000496676.5 link	n.1525G>C		non_coding_transcript_exon_variant	Exon 10 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30221

AN:

151884

Hom.:

3816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0519

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.207

GnomAD3 exomes

AF:

0.235

AC:

58518

AN:

248810

Hom.:

7626

AF XY:

0.245

AC XY:

33154

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.0480

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.274

Gnomad EAS exome

AF:

0.174

Gnomad SAS exome

AF:

0.296

Gnomad FIN exome

AF:

0.256

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

AF:

0.261

AC:

380898

AN:

1460146

Hom.:

51524

Cov.:

AF XY:

0.263

AC XY:

191167

AN XY:

726416

show subpopulations

Gnomad4 AFR exome

AF:

0.0453

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.293

Gnomad4 FIN exome

AF:

0.255

Gnomad4 NFE exome

AF:

0.272

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.199

AC:

30217

AN:

152002

Hom.:

3819

Cov.:

AF XY:

0.201

AC XY:

14967

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0517

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.287

Gnomad4 FIN

AF:

0.262

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.208

Alfa

AF:

0.260

Hom.:

4121

Bravo

AF:

0.185

TwinsUK

AF:

0.288

AC:

1069

ALSPAC

AF:

0.279

AC:

1076

ESP6500AA

AF:

0.0586

AC:

219

ESP6500EA

AF:

0.264

AC:

2163

ExAC

AF:

0.235

AC:

28351

Asia WGS

AF:

0.232

AC:

808

AN:

3478

EpiCase

AF:

0.276

EpiControl

AF:

0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.42

DANN

Benign

0.45

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.22

PROVEAN

Benign

0.76

REVEL

Benign

0.035

Sift

Benign

0.24

Sift4G

Benign

0.55

Polyphen

0.0030

Vest4

0.029

MPC

0.18

ClinPred

0.00050

GERP RS

1.0

Varity_R

0.042

gMVP

0.065

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