dbSNP rs763348421: RNF212:p.Leu207Phe (chr4-1073147-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001131034.4(RNF212):c.621G>T(p.Leu207Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

RNF212
NM_001131034.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.443

Publications

2 publications found

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]

RNF212 Gene-Disease associations (from GenCC):

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

RNF212 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03290987).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131034.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF212	NM_001131034.4	MANE Select	c.621G>T	p.Leu207Phe	missense	Exon 10 of 10	NP_001124506.1	Q495C1-1
RNF212	NM_001366919.1		c.574+452G>T		intron	N/A	NP_001353848.1	A0A8V8TN20
RNF212	NM_194439.5		c.575-7G>T		splice_region intron	N/A	NP_919420.1	Q495C1-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF212	ENST00000433731.7	TSL:1 MANE Select	c.621G>T	p.Leu207Phe	missense	Exon 10 of 10	ENSP00000389709.2	Q495C1-1
RNF212	ENST00000382968.9	TSL:1	c.575-7G>T		splice_region intron	N/A	ENSP00000372428.5	Q495C1-5
RNF212	ENST00000698262.1		c.574+452G>T		intron	N/A	ENSP00000513634.1	A0A8V8TN20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000597

AC:

AN:

251464

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000815

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000554

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112004

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

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

Cov.:

Alfa

AF:

0.0000385

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.2

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.013

Eigen

Benign

-0.88

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.31

M_CAP

Benign

0.0043

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.44

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.40

REVEL

Benign

0.042

Sift

Uncertain

0.020

Sift4G

Benign

0.21

Polyphen

0.55

Vest4

0.029

MutPred

0.23

Loss of glycosylation at P211 (P = 0.0578)

MVP

0.58

MPC

0.15

ClinPred

0.045

GERP RS

1.1

Varity_R

0.066

gMVP

0.047

Mutation Taster

=98/2

polymorphism

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over