Genetic Variant NM_001131034.4:c.827C>T (chr4-1072941-G-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.827C>T(p.Thr276Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,613,918 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: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

RNF212
NM_001131034.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.43

Publications

0 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=0.03307724).

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.827C>T	p.Thr276Met	missense	Exon 10 of 10	NP_001124506.1	Q495C1-1
RNF212	NM_194439.5		c.*75C>T		3_prime_UTR	Exon 10 of 10	NP_919420.1	Q495C1-5
RNF212	NM_001366919.1		c.574+658C>T		intron	N/A	NP_001353848.1	A0A8V8TN20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF212	ENST00000433731.7	TSL:1 MANE Select	c.827C>T	p.Thr276Met	missense	Exon 10 of 10	ENSP00000389709.2	Q495C1-1
RNF212	ENST00000382968.9	TSL:1	c.*75C>T		3_prime_UTR	Exon 10 of 10	ENSP00000372428.5	Q495C1-5
RNF212	ENST00000698262.1		c.574+658C>T		intron	N/A	ENSP00000513634.1	A0A8V8TN20

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000557

AC:

AN:

251138

AF XY:

0.0000589

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000969

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000119

AC:

174

AN:

1461624

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33474

American (AMR)

AF:

0.0000224

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000145

AC:

161

AN:

1111786

Other (OTH)

AF:

0.000133

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.0000788

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

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:

0.000141

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.10

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0098

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.36

M_CAP

Benign

0.0045

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-1.4

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.19

REVEL

Benign

0.075

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.024

MVP

0.40

MPC

0.18

ClinPred

0.023

GERP RS

-0.52

Varity_R

0.026

gMVP

0.053

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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