1-103534857-G-C

Position:

• chr1-103534857-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_017619.4(RNPC3):​c.443G>C​(p.Gly148Ala) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNPC3 NM_017619.4 missense, splice_region
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.68

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-103534857-G-C is Pathogenic according to our data. Variant chr1-103534857-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 1319999.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNPC3	NM_017619.4	c.443G>C	p.Gly148Ala	missense_variant, splice_region_variant	4/15	ENST00000423855.7	NP_060089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNPC3	ENST00000423855.7	c.443G>C	p.Gly148Ala	missense_variant, splice_region_variant	4/15	1	NM_017619.4	ENSP00000391432	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Isolated growth hormone deficiency, type 5 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T;T;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;.;D
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.56	D;D;D;D
MetaSVM	Benign	-0.76	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0060	D;D;D;D
Sift4G	Uncertain	0.043	D;D;D;D
Polyphen		1.0	.;.;D;D
Vest4		0.59
MutPred		0.35		Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);
MVP		0.53
MPC		0.43
ClinPred		0.98	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.38		Position offset: 0

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: chr1-104077479;