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GeneBe

6-33211285-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002931.4(RING1):c.583G>A(p.Ala195Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000683 in 1,611,236 control chromosomes in the GnomAD database, including 4 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00069 ( 4 hom. )

Consequence

RING1
NM_002931.4 missense

Scores

1
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.633
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0042042136).
BP6
Variant 6-33211285-G-A is Benign according to our data. Variant chr6-33211285-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2229718.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd at 100 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RING1NM_002931.4 linkuse as main transcriptc.583G>A p.Ala195Thr missense_variant 5/7 ENST00000374656.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RING1ENST00000374656.5 linkuse as main transcriptc.583G>A p.Ala195Thr missense_variant 5/71 NM_002931.4 P1Q06587-1
RING1ENST00000478431.1 linkuse as main transcriptn.571G>A non_coding_transcript_exon_variant 3/51

Frequencies

GnomAD3 genomes
AF:
0.000660
AC:
100
AN:
151438
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00807
Gnomad EAS
AF:
0.000195
Gnomad SAS
AF:
0.00125
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000545
Gnomad OTH
AF:
0.000960
GnomAD3 exomes
AF:
0.000919
AC:
225
AN:
244950
Hom.:
1
AF XY:
0.00101
AC XY:
135
AN XY:
133784
show subpopulations
Gnomad AFR exome
AF:
0.000134
Gnomad AMR exome
AF:
0.00119
Gnomad ASJ exome
AF:
0.00737
Gnomad EAS exome
AF:
0.000110
Gnomad SAS exome
AF:
0.000922
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000667
Gnomad OTH exome
AF:
0.000991
GnomAD4 exome
AF:
0.000687
AC:
1003
AN:
1459698
Hom.:
4
Cov.:
33
AF XY:
0.000737
AC XY:
535
AN XY:
726156
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00112
Gnomad4 ASJ exome
AF:
0.00896
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000615
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000473
Gnomad4 OTH exome
AF:
0.00118
GnomAD4 genome
AF:
0.000647
AC:
98
AN:
151538
Hom.:
0
Cov.:
31
AF XY:
0.000688
AC XY:
51
AN XY:
74078
show subpopulations
Gnomad4 AFR
AF:
0.0000243
Gnomad4 AMR
AF:
0.00151
Gnomad4 ASJ
AF:
0.00807
Gnomad4 EAS
AF:
0.000195
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000545
Gnomad4 OTH
AF:
0.000950
Alfa
AF:
0.00113
Hom.:
1
Bravo
AF:
0.000759
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000331
AC:
1
ESP6500EA
AF:
0.000555
AC:
3
ExAC
AF:
0.000861
AC:
101
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00109
EpiControl
AF:
0.00119

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 28, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.47
Cadd
Benign
18
Dann
Benign
0.85
DEOGEN2
Benign
0.041
T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.57
D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.0042
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
0.94
D
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
0.73
N
REVEL
Benign
0.072
Sift
Benign
0.61
T
Sift4G
Benign
0.78
T
Polyphen
0.0
B
Vest4
0.16
MVP
0.38
MPC
0.55
ClinPred
0.0047
T
GERP RS
1.3
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.043
gMVP
0.12

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: rs149445528; hg19: chr6-33179062; COSMIC: COSV63002273; COSMIC: COSV63002273; API