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GeneBe

6-33211451-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

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

7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34
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 Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.34002793).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RING1NM_002931.4 linkuse as main transcriptc.749C>T p.Pro250Leu missense_variant 5/7 ENST00000374656.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RING1ENST00000374656.5 linkuse as main transcriptc.749C>T p.Pro250Leu missense_variant 5/71 NM_002931.4 P1Q06587-1
RING1ENST00000478431.1 linkuse as main transcriptn.737C>T non_coding_transcript_exon_variant 3/51

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000473
AC:
1
AN:
211512
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
117038
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:
0.0000109
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000201
AC:
29
AN:
1442440
Hom.:
1
Cov.:
36
AF XY:
0.0000167
AC XY:
12
AN XY:
716880
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000257
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000136
Gnomad4 OTH exome
AF:
0.000218
GnomAD4 genome
Cov.:
32
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsFeb 15, 2023The c.749C>T (p.P250L) alteration is located in exon 5 (coding exon 4) of the RING1 gene. This alteration results from a C to T substitution at nucleotide position 749, causing the proline (P) at amino acid position 250 to be replaced by a leucine (L). 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
0.11
BayesDel_addAF
Benign
0.0035
T
BayesDel_noAF
Benign
-0.23
Cadd
Uncertain
24
Dann
Uncertain
0.99
DEOGEN2
Benign
0.11
T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Benign
0.75
D
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.34
T
MetaSVM
Uncertain
-0.25
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-1.8
N
REVEL
Uncertain
0.41
Sift
Benign
0.073
T
Sift4G
Benign
0.26
T
Polyphen
1.0
D
Vest4
0.41
MutPred
0.30
Loss of glycosylation at P250 (P = 0.0059);
MVP
0.65
MPC
0.58
ClinPred
0.86
D
GERP RS
4.2
Varity_R
0.21
gMVP
0.44

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

LitVar

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

Other links and lift over

dbSNP: rs879047310; hg19: chr6-33179228; API