dbSNP rs764724224: RC3H2:p.Pro1135Arg (chr9-122849799-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001100588.3(RC3H2):c.3404C>G(p.Pro1135Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000447 in 1,566,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

RC3H2
NM_001100588.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.41

Publications

5 publications found

Variant links:

Genes affected

RC3H2 (HGNC:21461): (ring finger and CCCH-type domains 2) Enables nucleic acid binding activity and ubiquitin protein ligase activity. Involved in protein polyubiquitination. Located in cell surface; intracellular membrane-bounded organelle; and membrane. [provided by Alliance of Genome Resources, Apr 2022]

RC3H2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100588.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RC3H2	NM_001100588.3	MANE Select	c.3404C>G	p.Pro1135Arg	missense	Exon 21 of 21	NP_001094058.1	Q9HBD1-1
RC3H2	NM_001354482.2		c.3290C>G	p.Pro1097Arg	missense	Exon 20 of 20	NP_001341411.1
RC3H2	NM_001354479.2		c.3233C>G	p.Pro1078Arg	missense	Exon 20 of 20	NP_001341408.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RC3H2	ENST00000357244.7	TSL:5 MANE Select	c.3404C>G	p.Pro1135Arg	missense	Exon 21 of 21	ENSP00000349783.2	Q9HBD1-1
RC3H2	ENST00000373670.5	TSL:5	c.3404C>G	p.Pro1135Arg	missense	Exon 20 of 20	ENSP00000362774.1	Q9HBD1-1
RC3H2	ENST00000954280.1		c.3404C>G	p.Pro1135Arg	missense	Exon 22 of 22	ENSP00000624339.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000142

AC:

AN:

211252

AF XY:

0.0000173

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000430

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000353

AC:

AN:

1414902

Hom.:

Cov.:

AF XY:

0.00000427

AC XY:

AN XY:

703246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30910

American (AMR)

AF:

0.0000293

AC:

AN:

34172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24032

East Asian (EAS)

AF:

0.0000523

AC:

AN:

38236

South Asian (SAS)

AF:

0.00

AC:

AN:

78776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5530

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1092720

Other (OTH)

AF:

0.00

AC:

AN:

58086

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:

0.0000132

AC:

AN:

151978

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41372

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000227

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

0.14

PhyloP100

6.4

Varity_R

0.19

gMVP

0.27

Mutation Taster

=87/13

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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