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GeneBe

6-33211908-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002931.4(RING1):c.1025G>A(p.Gly342Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,450,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

RING1
NM_002931.4 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.780
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1369263).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RING1NM_002931.4 linkuse as main transcriptc.1025G>A p.Gly342Asp missense_variant 6/7 ENST00000374656.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RING1ENST00000374656.5 linkuse as main transcriptc.1025G>A p.Gly342Asp missense_variant 6/71 NM_002931.4 P1Q06587-1
RING1ENST00000478431.1 linkuse as main transcriptn.1013G>A non_coding_transcript_exon_variant 4/51

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000882
AC:
2
AN:
226706
Hom.:
0
AF XY:
0.00000812
AC XY:
1
AN XY:
123126
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000199
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000276
AC:
4
AN:
1450828
Hom.:
0
Cov.:
37
AF XY:
0.00000277
AC XY:
2
AN XY:
721080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000361
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000826
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 05, 2022The c.1025G>A (p.G342D) alteration is located in exon 6 (coding exon 5) of the RING1 gene. This alteration results from a G to A substitution at nucleotide position 1025, causing the glycine (G) at amino acid position 342 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
0.0073
T
BayesDel_noAF
Benign
-0.20
Cadd
Benign
19
Dann
Benign
0.97
DEOGEN2
Benign
0.046
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.29
N
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
0.87
N
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.15
N
REVEL
Benign
0.28
Sift
Benign
0.17
T
Sift4G
Uncertain
0.018
D
Polyphen
0.023
B
Vest4
0.42
MutPred
0.23
Gain of solvent accessibility (P = 0.0638);
MVP
0.83
MPC
0.74
ClinPred
0.081
T
GERP RS
2.1
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.2
Varity_R
0.18
gMVP
0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780016095; hg19: chr6-33179685; API