rs12981

Positions:

• chr9-122844732-T-A
• chr9-122844732-T-C
• chr9-122844732-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001100588.3(RC3H2):​c.*4895A>T variant causes a 3 prime UTR 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: RC3H2 NM_001100588.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460

Genes affected

RC3H2 (HGNC:21461): (ring finger and CCCH-type domains 2) Enables nucleic acid binding activity and ubiquitin protein ligase activity. Involved in protein polyubiquitination. Located in cell surface; intracellular membrane-bounded organelle; and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RC3H2	NM_001100588.3	c.*4895A>T		3_prime_UTR_variant	21/21	ENST00000357244.7	NP_001094058.1
RC3H2	NM_001354478.2	c.*5062A>T		3_prime_UTR_variant	21/21		NP_001341407.1
RC3H2	NM_001354479.2	c.*4895A>T		3_prime_UTR_variant	20/20		NP_001341408.1
RC3H2	NM_001354482.2	c.*4895A>T		3_prime_UTR_variant	20/20		NP_001341411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RC3H2	ENST00000357244.7	c.*4895A>T		3_prime_UTR_variant	21/21	5	NM_001100588.3	ENSP00000349783	P1
RC3H2	ENST00000373670.5	c.*4895A>T		3_prime_UTR_variant	20/20	5		ENSP00000362774	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.4
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12981; hg19: chr9-125607011;