Genetic Variant NM_002931.4:c.749C>T (chr6-33211451-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_002931.4(RING1):c.749C>T(p.Pro250Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 1,442,440 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000020 ( 1 hom. )

Consequence

RING1
NM_002931.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

Publications

0 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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34002793).

BS2

High AC in GnomAdExome4 at 29 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.749C>T	p.Pro250Leu	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.749C>T	p.Pro250Leu	missense	Exon 5 of 7	ENSP00000363787.4	Q06587-1
RING1	ENST00000478431.1	TSL:1	n.737C>T		non_coding_transcript_exon	Exon 3 of 5
RING1	ENST00000869802.1		c.749C>T	p.Pro250Leu	missense	Exon 4 of 6	ENSP00000539861.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000473

AC:

AN:

211512

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000109

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1442440

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

716880

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33012

American (AMR)

AF:

0.00

AC:

AN:

41744

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25702

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38852

South Asian (SAS)

AF:

0.00

AC:

AN:

84682

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.0000136

AC:

AN:

1102384

Other (OTH)

AF:

0.000218

AC:

AN:

59584

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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.:

Asia WGS

AF:

0.000289

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

0.11

BayesDel_addAF

Benign

0.0035

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.75

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.34

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

0.0

PhyloP100

2.3

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.41

Sift

Benign

0.073

Sift4G

Benign

0.26

Polyphen

1.0

Vest4

0.41

MutPred

0.30

Loss of glycosylation at P250 (P = 0.0059)

MVP

0.65

MPC

0.58

ClinPred

0.86

GERP RS

4.2

Varity_R

0.21

gMVP

0.44

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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