dbSNP rs572675416: RNF212:p.Arg257GlyfsTer15 (chr4-1056882-CG-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001366919.1(RNF212):c.769delC(p.Arg257GlyfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 985,294 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

RNF212
NM_001366919.1 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

0 publications found

Variant links:

COSMIC-nc: COSV101540027

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]

RNF212 Gene-Disease associations (from GenCC):

spermatogenic failure 62
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

RNF212 links:

ENSG00000294272 (HGNC:):

ENSG00000294272 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366919.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF212	NM_001366919.1		c.769delC	p.Arg257GlyfsTer15	frameshift	Exon 11 of 12	NP_001353848.1	A0A8V8TN20
	RNF212	NM_001366918.1		c.648-380delC		intron	N/A	NP_001353847.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF212	ENST00000698262.1		c.769delC	p.Arg257GlyfsTer15	frameshift	Exon 11 of 12	ENSP00000513634.1	A0A8V8TN20
RNF212	ENST00000505693.5	TSL:5	n.696delC		non_coding_transcript_exon	Exon 5 of 6
RNF212	ENST00000508633.5	TSL:3	n.351delC		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000840

AC:

AN:

833284

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

385032

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15814

American (AMR)

AF:

0.00

AC:

AN:

990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5128

East Asian (EAS)

AF:

0.00

AC:

AN:

3622

South Asian (SAS)

AF:

0.000121

AC:

AN:

16496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3248

European-Non Finnish (NFE)

AF:

0.00000526

AC:

AN:

759974

Other (OTH)

AF:

0.0000365

AC:

AN:

27390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

41360

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over