Variant 1-6209164-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_207396.3(RNF207):c.519G>A(p.Leu173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,557,504 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

RNF207
NM_207396.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.37

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:

RPL22 (HGNC:10315): (ribosomal protein L22) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a cytoplasmic ribosomal protein that is a component of the 60S subunit. The protein belongs to the L22E family of ribosomal proteins. Its initiating methionine residue is post-translationally removed. The protein can bind specifically to Epstein-Barr virus-encoded RNAs (EBERs) 1 and 2. The mouse protein has been shown to be capable of binding to heparin. Transcript variants utilizing alternative polyA signals exist. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. It was previously thought that this gene mapped to 3q26 and that it was fused to the acute myeloid leukemia 1 (AML1) gene located at 21q22 in some therapy-related myelodysplastic syndrome patients with 3;21 translocations; however, these fusions actually involve a ribosomal protein L22 pseudogene located at 3q26, and this gene actually maps to 1p36.3-p36.2. [provided by RefSeq, Jul 2008]

RPL22 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-6209164-G-A is Benign according to our data. Variant chr1-6209164-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 729039.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.37 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF207	NM_207396.3 linkuse as main transcript	c.519G>A	p.Leu173=	synonymous_variant	5/18	ENST00000377939.5	NP_997279.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF207	ENST00000377939.5 linkuse as main transcript	c.519G>A	p.Leu173=	synonymous_variant	5/18	5	NM_207396.3	ENSP00000367173	P1	Q6ZRF8-1

Frequencies

GnomAD3 genomes

AF:

0.000815

AC:

124

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000734

AC:

117

AN:

159374

Hom.:

AF XY:

0.000664

AC XY:

AN XY:

85812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00129

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000576

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.000682

GnomAD4 exome

AF:

0.00114

AC:

1598

AN:

1405154

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

779

AN XY:

693812

show subpopulations

Gnomad4 AFR exome

AF:

0.000311

Gnomad4 AMR exome

AF:

0.000976

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000478

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.00143

GnomAD4 genome

AF:

0.000814

AC:

124

AN:

152350

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.000839

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over