9-122844732-T-C

Variant names:

• chr9-122844732-T-C
• rs12981
• NM_001100588.3:c.*4895A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000357244.7(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 ENST00000357244.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000357244.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RC3H2	NM_001100588.3	MANE Select	c.*4895A>G		3_prime_UTR	Exon 21 of 21	NP_001094058.1
	RC3H2	NM_001354482.2		c.*4895A>G		3_prime_UTR	Exon 20 of 20	NP_001341411.1
	RC3H2	NM_001354479.2		c.*4895A>G		3_prime_UTR	Exon 20 of 20	NP_001341408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RC3H2	ENST00000357244.7	TSL:5 MANE Select	c.*4895A>G		3_prime_UTR	Exon 21 of 21	ENSP00000349783.2
	RC3H2	ENST00000373670.5	TSL:5	c.*4895A>G		3_prime_UTR	Exon 20 of 20	ENSP00000362774.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.347 AC: 14377 AN: 41452

American (AMR) AF: 0.315 AC: 4814 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 609 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3364 AN: 5164

South Asian (SAS) AF: 0.127 AC: 612 AN: 4814

European-Finnish (FIN) AF: 0.168 AC: 1777 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8521 AN: 67980

Other (OTH) AF: 0.227 AC: 480 AN: 2114

Alfa AF: 0.176 Hom.: 922

Bravo AF: 0.252

Asia WGS AF: 0.389 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.8
DANN	Benign	0.80
PhyloP100		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12981; hg19: chr9-125607011;