dbSNP rs4045481: RNF212:p.Thr58Thr (chr4-1096837-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001131034.4(RNF212):c.174C>T(p.Thr58Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 1,601,476 control chromosomes in the GnomAD database, including 353,627 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 27016 hom., cov: 33)

Exomes 𝑓: 0.67 ( 326611 hom. )

Consequence

RNF212
NM_001131034.4 splice_region, synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.10

Publications

34 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.05).

BP7

Synonymous conserved (PhyloP=-5.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF212	NM_001131034.4 link	c.174C>T	p.Thr58Thr	splice_region_variant, synonymous_variant	Exon 3 of 10	ENST00000433731.7	NP_001124506.1	Q495C1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF212	ENST00000433731.7 link	c.174C>T	p.Thr58Thr	splice_region_variant, synonymous_variant	Exon 3 of 10	1	NM_001131034.4	ENSP00000389709.2		Q495C1-1

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87681

AN:

152036

Hom.:

27022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.720

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.689

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.685

Gnomad OTH

AF:

0.605

GnomAD2 exomes

AF:

0.637

AC:

160157

AN:

251362

AF XY:

0.649

show subpopulations

Gnomad AFR exome

AF:

0.339

Gnomad AMR exome

AF:

0.545

Gnomad ASJ exome

AF:

0.718

Gnomad EAS exome

AF:

0.617

Gnomad FIN exome

AF:

0.677

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.655

GnomAD4 exome

AF:

0.667

AC:

967293

AN:

1449322

Hom.:

326611

Cov.:

AF XY:

0.670

AC XY:

483352

AN XY:

721776

show subpopulations

African (AFR)

AF:

0.333

AC:

11092

AN:

33320

American (AMR)

AF:

0.548

AC:

24506

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.716

AC:

18654

AN:

26050

East Asian (EAS)

AF:

0.576

AC:

22827

AN:

39632

South Asian (SAS)

AF:

0.692

AC:

59536

AN:

85984

European-Finnish (FIN)

AF:

0.678

AC:

36184

AN:

53354

Middle Eastern (MID)

AF:

0.696

AC:

3999

AN:

5746

European-Non Finnish (NFE)

AF:

0.683

AC:

751455

AN:

1100616

Other (OTH)

AF:

0.651

AC:

39040

AN:

59934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

14395

28790

43185

57580

71975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19050

38100

57150

76200

95250

<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:

0.576

AC:

87698

AN:

152154

Hom.:

27016

Cov.:

AF XY:

0.578

AC XY:

43001

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.346

AC:

14357

AN:

41482

American (AMR)

AF:

0.564

AC:

8625

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.720

AC:

2501

AN:

3472

East Asian (EAS)

AF:

0.619

AC:

3202

AN:

5174

South Asian (SAS)

AF:

0.689

AC:

3319

AN:

4820

European-Finnish (FIN)

AF:

0.678

AC:

7186

AN:

10596

Middle Eastern (MID)

AF:

0.663

AC:

195

AN:

294

European-Non Finnish (NFE)

AF:

0.685

AC:

46595

AN:

68002

Other (OTH)

AF:

0.605

AC:

1280

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1798

3597

5395

7194

8992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.637

Hom.:

83006

Bravo

AF:

0.554

Asia WGS

AF:

0.605

AC:

2102

AN:

3478

EpiCase

AF:

0.674

EpiControl

AF:

0.671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0090

(source)

DANN

Benign

0.64

PhyloP100

-5.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.040

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over