chr9-122844732-T-C

Position:

• chr9-122844732-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100588.3(RC3H2):​c.*4895A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,076 control chromosomes in the GnomAD database, including 5,357 homozygotes. 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: 𝑓 0.23 (5357 hom., cov: 32)
  • Exomes 𝑓: 0.20 (0 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RC3H2	NM_001100588.3	c.*4895A>G		3_prime_UTR_variant	21/21	ENST00000357244.7	NP_001094058.1
RC3H2	NM_001354478.2	c.*5062A>G		3_prime_UTR_variant	21/21		NP_001341407.1
RC3H2	NM_001354479.2	c.*4895A>G		3_prime_UTR_variant	20/20		NP_001341408.1
RC3H2	NM_001354482.2	c.*4895A>G		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>G		3_prime_UTR_variant	21/21	5	NM_001100588.3	ENSP00000349783	P1
RC3H2	ENST00000373670.5	c.*4895A>G		3_prime_UTR_variant	20/20	5		ENSP00000362774	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34550 AN: 151948 Hom.: 5323 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.228 AC: 34651 AN: 152066 Hom.: 5357 Cov.: 32 AF XY: 0.233 AC XY: 17317 AN XY: 74360

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.227

Alfa AF: 0.166 Hom.: 749

Bravo AF: 0.252

Asia WGS AF: 0.389 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.8
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;