chr9-122844338-T-C

Variant names:

• chr9-122844338-T-C
• rs10985794
• NM_001100588.3:c.*5289A>G

Variant summary

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

The NM_001100588.3(RC3H2):​c.*5289A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 152,266 control chromosomes in the GnomAD database, including 138 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 0.028 (138 hom., cov: 32)
• Consequence: RC3H2 NM_001100588.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RC3H2	NM_001100588.3	c.*5289A>G		downstream_gene_variant		ENST00000357244.7	NP_001094058.1
RC3H2	NM_001354482.2	c.*5289A>G		downstream_gene_variant			NP_001341411.1
RC3H2	NM_001354479.2	c.*5289A>G		downstream_gene_variant			NP_001341408.1
RC3H2	NM_001354478.2	c.*5456A>G		downstream_gene_variant			NP_001341407.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RC3H2	ENST00000357244.7	c.*5289A>G		downstream_gene_variant		5	NM_001100588.3	ENSP00000349783.2
RC3H2	ENST00000373670.5	c.*5289A>G		downstream_gene_variant		5		ENSP00000362774.1

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4198 AN: 152148 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.00519

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0868

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0276 AC: 4199 AN: 152266 Hom.: 138 Cov.: 32 AF XY: 0.0290 AC XY: 2156 AN XY: 74458

African (AFR) AF: 0.00517 AC: 215 AN: 41558

American (AMR) AF: 0.0263 AC: 402 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.179 AC: 927 AN: 5174

South Asian (SAS) AF: 0.0867 AC: 417 AN: 4810

European-Finnish (FIN) AF: 0.0215 AC: 228 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0273 AC: 1859 AN: 68008

Other (OTH) AF: 0.0260 AC: 55 AN: 2116

Alfa AF: 0.0296 Hom.: 221

Bravo AF: 0.0261

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.63
DANN	Benign	0.84
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10985794; hg19: chr9-125606617;