NM_002931.4:c.749C>A

Variant names:

• chr6-33211451-C-A
• rs879047310
• NM_002931.4:c.749C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002931.4(RING1):​c.749C>A​(p.Pro250His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RING1 NM_002931.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.34

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33421).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RING1	NM_002931.4	c.749C>A	p.Pro250His	missense_variant	Exon 5 of 7	ENST00000374656.5	NP_002922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RING1	ENST00000374656.5	c.749C>A	p.Pro250His	missense_variant	Exon 5 of 7	1	NM_002931.4	ENSP00000363787.4
RING1	ENST00000478431.1	n.737C>A		non_coding_transcript_exon_variant	Exon 3 of 5	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.90	N
REVEL	Uncertain	0.39
Sift	Benign	0.037	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.43
MutPred		0.25		Loss of glycosylation at P250 (P = 0.0059);
MVP		0.59
MPC		0.66
ClinPred		0.88	D
GERP RS		4.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
Varity_R		0.21
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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

Other links and lift over

dbSNP: rs879047310; hg19: chr6-33179228;