Genetic Variant RING1:p.Gly209Val (chr6-33211328-G-T) – 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_002931.4(RING1):c.626G>T(p.Gly209Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,458,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G209A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

RING1
NM_002931.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

Publications

1 publications found

Variant links:

Genes affected

RING1 (HGNC:10018): (ring finger protein 1) This gene belongs to the RING finger family, members of which encode proteins characterized by a RING domain, a zinc-binding motif related to the zinc finger domain. The gene product can bind DNA and can act as a transcriptional repressor. It is associated with the multimeric polycomb group protein complex. The gene product interacts with the polycomb group proteins BMI1, EDR1, and CBX4, and colocalizes with these proteins in large nuclear domains. It interacts with the CBX4 protein via its glycine-rich C-terminal domain. The gene maps to the HLA class II region, where it is contiguous with the RING finger genes FABGL and HKE4. [provided by RefSeq, Jul 2008]

RING1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Illumina, Ambry Genetics

RING1 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 22 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002931.4. 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
	RING1	NM_002931.4	MANE Select	c.626G>T	p.Gly209Val	missense	Exon 5 of 7	NP_002922.2	A0A1U9X8F2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RING1	ENST00000374656.5	TSL:1 MANE Select	c.626G>T	p.Gly209Val	missense	Exon 5 of 7	ENSP00000363787.4	Q06587-1
RING1	ENST00000478431.1	TSL:1	n.614G>T		non_coding_transcript_exon	Exon 3 of 5
RING1	ENST00000869802.1		c.626G>T	p.Gly209Val	missense	Exon 4 of 6	ENSP00000539861.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000341

AC:

AN:

234822

AF XY:

0.0000386

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000566

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000583

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1458140

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725254

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

44380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39646

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5284

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1110844

Other (OTH)

AF:

0.0000332

AC:

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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:

0.0000434

Hom.:

ExAC

AF:

0.0000346

AC:

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

0.12

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.067

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.81

M_CAP

Pathogenic

0.43

MetaRNN

Uncertain

0.54

MetaSVM

Uncertain

0.52

MutationAssessor

Benign

0.0

PhyloP100

3.9

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.66

REVEL

Uncertain

0.44

Sift

Benign

0.34

Sift4G

Benign

0.30

Polyphen

1.0

Vest4

0.44

MutPred

0.39

Gain of sheet (P = 0.0061)

MVP

0.86

MPC

0.71

ClinPred

0.18

GERP RS

4.3

Varity_R

0.17

gMVP

0.35

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over