rs918108896

Variant names:

• chr1-103551730-C-A
• rs918108896
• NM_017619.4:c.1504C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-103551730-C-A
• chr1-103551730-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_017619.4(RNPC3):​c.1504C>A​(p.Arg502Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,375,920 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: RNPC3 NM_017619.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 0 publications found

Genes affected

RNPC3 (HGNC:18666): (RNA binding region (RNP1, RRM) containing 3) Two types of spliceosomes catalyze splicing of pre-mRNAs. The major U2-type spliceosome is found in all eukaryotes and removes U2-type introns, which represent more than 99% of pre-mRNA introns. The minor U12-type spliceosome is found in some eukaryotes and removes U12-type introns, which are rare and have distinct splice consensus signals. The U12-type spliceosome consists of several small nuclear RNAs and associated proteins. This gene encodes a 65K protein that is a component of the U12-type spliceosome. This protein contains two RNA recognition motifs (RRMs), suggesting that it may contact one of the small nuclear RNAs of the minor spliceosome. [provided by RefSeq, Jul 2008]

RNPC3 Gene-Disease associations (from GenCC):

• isolated growth hormone deficiency, type 5

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• isolated growth hormone deficiency type IA

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BP7: Synonymous conserved (PhyloP=3.31 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017619.4. 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
	RNPC3	NM_017619.4	MANE Select	c.1504C>A	p.Arg502Arg	synonymous	Exon 14 of 15	NP_060089.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPC3	ENST00000423855.7	TSL:1 MANE Select	c.1504C>A	p.Arg502Arg	synonymous	Exon 14 of 15	ENSP00000391432.1
	RNPC3	ENST00000533834.1	TSL:1	n.2610C>A		non_coding_transcript_exon	Exon 6 of 6
	RNPC3	ENST00000533099.5	TSL:5	c.1504C>A	p.Arg502Arg	synonymous	Exon 15 of 16	ENSP00000432886.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1375920 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 679126

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30410

American (AMR) AF: 0.00 AC: 0 AN: 32772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24842

East Asian (EAS) AF: 0.00 AC: 0 AN: 35546

South Asian (SAS) AF: 0.00 AC: 0 AN: 75124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1065022

Other (OTH) AF: 0.00 AC: 0 AN: 57154

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs918108896; hg19: chr1-104094352;