4-1058337-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001366919.1(RNF212):c.631A>G(p.Met211Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 142,288 control chromosomes in the GnomAD database, including 49,395 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (49395 hom., cov: 28)
  • Exomes 𝑓: 0.68 (74337 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNF212 NM_001366919.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.80

Genes affected

RNF212 (HGNC:27729): (ring finger protein 212) This gene encodes a RING finger protein that may function as a ubiquitin ligase. The encoded protein may be involved in meiotic recombination. This gene is located within a linkage disequilibrium block and polymorphisms in this gene may influence recombination rates. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 4-1058337-T-C is Benign according to our data. Variant chr4-1058337-T-C is described in ClinVar as [Benign]. Clinvar id is 3046854.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF212	NM_001366919.1	c.631A>G	p.Met211Val	missense_variant	10/12
RNF212	NM_001366918.1	c.631A>G	p.Met211Val	missense_variant	10/11
RNF212	XM_047450083.1	c.529A>G	p.Met177Val	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF212	ENST00000698262.1	c.631A>G	p.Met211Val	missense_variant	10/12			P2
RNF212	ENST00000503206.5	n.204A>G		non_coding_transcript_exon_variant	4/5	3
RNF212	ENST00000505693.5	n.558A>G		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes AF: 0.824 AC: 117218 AN: 142172 Hom.: 49357 Cov.: 28

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.809

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.681 AC: 204917 AN: 300886 Hom.: 74337 Cov.: 0 AF XY: 0.680 AC XY: 94606 AN XY: 139186

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.669

Gnomad4 EAS exome AF: 0.516

Gnomad4 SAS exome AF: 0.638

Gnomad4 FIN exome AF: 0.759

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.665

GnomAD4 genome AF: 0.824 AC: 117308 AN: 142288 Hom.: 49395 Cov.: 28 AF XY: 0.820 AC XY: 56790 AN XY: 69250

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.808

Alfa AF: 0.690 Hom.: 2595

Bravo AF: 0.813

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

RNF212-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 07, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.0030
Dann	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11724371; hg19: chr4-1052125;