rs879047310

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-33211451-C-A
• chr6-33211451-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P250L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RING1 NM_002931.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.34
• Publications: 0 publications found

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]

RING1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Illumina, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002931.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RING1	NM_002931.4	MANE Select	c.749C>A	p.Pro250His	missense	Exon 5 of 7	NP_002922.2	A0A1U9X8F2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RING1	ENST00000374656.5	TSL:1 MANE Select	c.749C>A	p.Pro250His	missense	Exon 5 of 7	ENSP00000363787.4	Q06587-1
	RING1	ENST00000478431.1	TSL:1	n.737C>A		non_coding_transcript_exon	Exon 3 of 5
	RING1	ENST00000869802.1		c.749C>A	p.Pro250His	missense	Exon 4 of 6	ENSP00000539861.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.3
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
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs879047310; hg19: chr6-33179228;