6-33211328-G-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -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
NM_002931.4 missense
Scores
1
9
8
Clinical Significance
Conservation
PhyloP100: 3.94
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 Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RING1 | NM_002931.4 | c.626G>T | p.Gly209Val | missense_variant | 5/7 | ENST00000374656.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RING1 | ENST00000374656.5 | c.626G>T | p.Gly209Val | missense_variant | 5/7 | 1 | NM_002931.4 | P1 | |
RING1 | ENST00000478431.1 | n.614G>T | non_coding_transcript_exon_variant | 3/5 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD3 exomes AF: 0.0000341 AC: 8AN: 234822Hom.: 0 AF XY: 0.0000386 AC XY: 5AN XY: 129398
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1458140Hom.: 0 Cov.: 35 AF XY: 0.0000165 AC XY: 12AN XY: 725254
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GnomAD4 genome ? Cov.: 30
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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 submitter | clinical testing | Ambry Genetics | Oct 27, 2022 | The c.626G>T (p.G209V) alteration is located in exon 5 (coding exon 4) of the RING1 gene. This alteration results from a G to T substitution at nucleotide position 626, causing the glycine (G) at amino acid position 209 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of sheet (P = 0.0061);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at