9-122880408-G-A

Variant names:

• chr9-122880408-G-A
• rs2251495
• NM_001100588.3:c.960+186C>T

Variant summary

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

The NM_001100588.3(RC3H2):​c.960+186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 675,220 control chromosomes in the GnomAD database, including 223,144 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 0.74 (43597 hom., cov: 31)
  • Exomes 𝑓: 0.81 (179547 hom.)
• Consequence: RC3H2 NM_001100588.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 5 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]

SNORD90 (HGNC:32751): (small nucleolar RNA, C/D box 90)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100588.3. 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.960+186C>T		intron	N/A	NP_001094058.1
	RC3H2	NM_001354482.2		c.960+186C>T		intron	N/A	NP_001341411.1
	RC3H2	NM_001354479.2		c.960+186C>T		intron	N/A	NP_001341408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RC3H2	ENST00000357244.7	TSL:5 MANE Select	c.960+186C>T		intron	N/A	ENSP00000349783.2
	RC3H2	ENST00000335387.9	TSL:1	c.960+186C>T		intron	N/A	ENSP00000335150.5
	RC3H2	ENST00000373670.5	TSL:5	c.960+186C>T		intron	N/A	ENSP00000362774.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112228 AN: 151934 Hom.: 43607 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.759

GnomAD4 exome AF: 0.814 AC: 425666 AN: 523166 Hom.: 179547 Cov.: 6 AF XY: 0.821 AC XY: 229577 AN XY: 279600

African (AFR) AF: 0.533 AC: 7249 AN: 13602

American (AMR) AF: 0.617 AC: 12855 AN: 20836

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 12922 AN: 15454

East Asian (EAS) AF: 0.297 AC: 9618 AN: 32382

South Asian (SAS) AF: 0.887 AC: 44906 AN: 50618

European-Finnish (FIN) AF: 0.842 AC: 26814 AN: 31854

Middle Eastern (MID) AF: 0.845 AC: 1826 AN: 2160

European-Non Finnish (NFE) AF: 0.875 AC: 286743 AN: 327592

Other (OTH) AF: 0.793 AC: 22733 AN: 28668

GnomAD4 genome AF: 0.738 AC: 112232 AN: 152054 Hom.: 43597 Cov.: 31 AF XY: 0.733 AC XY: 54527 AN XY: 74348

African (AFR) AF: 0.533 AC: 22079 AN: 41418

American (AMR) AF: 0.671 AC: 10240 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2862 AN: 3472

East Asian (EAS) AF: 0.349 AC: 1805 AN: 5172

South Asian (SAS) AF: 0.873 AC: 4209 AN: 4824

European-Finnish (FIN) AF: 0.833 AC: 8807 AN: 10572

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.875 AC: 59528 AN: 68020

Other (OTH) AF: 0.754 AC: 1595 AN: 2114

Alfa AF: 0.758 Hom.: 3836

Bravo AF: 0.709

Asia WGS AF: 0.586 AC: 2042 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.46
PhyloP100		-0.014
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: rs2251495; hg19: chr9-125642687; COSMIC: COSV59012528; COSMIC: COSV59012528;