rs558832446

Variant names:

• chr9-122851405-T-A
• NM_001100588.3:c.3149A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-122851405-T-A
• chr9-122851405-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001100588.3(RC3H2):​c.3149A>T​(p.Asp1050Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1050G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RC3H2 NM_001100588.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.06

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RC3H2	NM_001100588.3	c.3149A>T	p.Asp1050Val	missense_variant	Exon 19 of 21	ENST00000357244.7	NP_001094058.1
RC3H2	NM_001354479.2	c.2978A>T	p.Asp993Val	missense_variant	Exon 18 of 20		NP_001341408.1
RC3H2	NM_001354478.2	c.3149A>T	p.Asp1050Val	missense_variant	Exon 19 of 21		NP_001341407.1
RC3H2	NM_001354482.2	c.3118-176A>T		intron_variant	Intron 18 of 19		NP_001341411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RC3H2	ENST00000357244.7	c.3149A>T	p.Asp1050Val	missense_variant	Exon 19 of 21	5	NM_001100588.3	ENSP00000349783.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.0029	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.27
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;D
Vest4		0.75
MutPred		0.39		Loss of solvent accessibility (P = 0.0299);Loss of solvent accessibility (P = 0.0299);
MVP		0.63
MPC		0.93
ClinPred		0.85	D
GERP RS		5.7
Varity_R		0.44
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-125613684;