4-1056882-C-CG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001366919.1(RNF212):​c.769dupC​(p.Arg257ProfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 985,460 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0044 ( 3 hom. )

Consequence

RNF212
NM_001366919.1 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF212NM_001366919.1 linkc.769dupC p.Arg257ProfsTer20 frameshift_variant Exon 11 of 12 NP_001353848.1
RNF212XM_047450083.1 linkc.667dupC p.Arg223ProfsTer20 frameshift_variant Exon 9 of 10 XP_047306039.1
RNF212XM_011513446.2 linkc.505dupC p.Arg169ProfsTer20 frameshift_variant Exon 6 of 7 XP_011511748.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF212ENST00000698262.1 linkc.769dupC p.Arg257ProfsTer20 frameshift_variant Exon 11 of 12 ENSP00000513634.1 A0A8V8TN20
RNF212ENST00000505693.5 linkn.696dupC non_coding_transcript_exon_variant Exon 5 of 6 5
RNF212ENST00000508633.5 linkn.351dupC non_coding_transcript_exon_variant Exon 3 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.00335
AC:
509
AN:
152008
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000943
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00321
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00579
Gnomad OTH
AF:
0.00287
GnomAD4 exome
AF:
0.00443
AC:
3692
AN:
833332
Hom.:
3
Cov.:
31
AF XY:
0.00437
AC XY:
1684
AN XY:
385050
show subpopulations
Gnomad4 AFR exome
AF:
0.000190
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00117
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00182
Gnomad4 FIN exome
AF:
0.00977
Gnomad4 NFE exome
AF:
0.00463
Gnomad4 OTH exome
AF:
0.00445
GnomAD4 genome
AF:
0.00335
AC:
510
AN:
152128
Hom.:
2
Cov.:
33
AF XY:
0.00312
AC XY:
232
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.000940
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.00321
Gnomad4 NFE
AF:
0.00580
Gnomad4 OTH
AF:
0.00284
Bravo
AF:
0.00277
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Spermatogenic failure 62 Uncertain:1
Oct 10, 2023
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs572675416; hg19: chr4-1050670; API