Variant 1-103533840-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017619.4(RNPC3):c.342C>T(p.Gly114=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 1,486,928 control chromosomes in the GnomAD database, including 294,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31072 hom., cov: 27)

Exomes 𝑓: 0.62 ( 262971 hom. )

Consequence

RNPC3
NM_017619.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.146

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 1-103533840-C-T is Benign according to our data. Variant chr1-103533840-C-T is described in ClinVar as [Benign]. Clinvar id is 1327962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.146 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNPC3	NM_017619.4 linkuse as main transcript	c.342C>T	p.Gly114=	synonymous_variant	3/15	ENST00000423855.7	NP_060089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNPC3	ENST00000423855.7 linkuse as main transcript	c.342C>T	p.Gly114=	synonymous_variant	3/15	1	NM_017619.4	ENSP00000391432	P4	Q96LT9-1

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

95960

AN:

149878

Hom.:

31050

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.494

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.668

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.726

Gnomad NFE

AF:

0.629

Gnomad OTH

AF:

0.669

GnomAD3 exomes

AF:

0.617

AC:

82581

AN:

133890

Hom.:

25873

AF XY:

0.621

AC XY:

44534

AN XY:

71734

show subpopulations

Gnomad AFR exome

AF:

0.726

Gnomad AMR exome

AF:

0.577

Gnomad ASJ exome

AF:

0.668

Gnomad EAS exome

AF:

0.383

Gnomad SAS exome

AF:

0.641

Gnomad FIN exome

AF:

0.591

Gnomad NFE exome

AF:

0.643

Gnomad OTH exome

AF:

0.642

GnomAD4 exome

AF:

0.623

AC:

832850

AN:

1336938

Hom.:

262971

Cov.:

AF XY:

0.623

AC XY:

412650

AN XY:

662034

show subpopulations

Gnomad4 AFR exome

AF:

0.730

Gnomad4 AMR exome

AF:

0.573

Gnomad4 ASJ exome

AF:

0.666

Gnomad4 EAS exome

AF:

0.342

Gnomad4 SAS exome

AF:

0.625

Gnomad4 FIN exome

AF:

0.586

Gnomad4 NFE exome

AF:

0.630

Gnomad4 OTH exome

AF:

0.628

GnomAD4 genome

AF:

0.640

AC:

96030

AN:

149990

Hom.:

31072

Cov.:

AF XY:

0.635

AC XY:

46436

AN XY:

73114

show subpopulations

Gnomad4 AFR

AF:

0.721

Gnomad4 AMR

AF:

0.600

Gnomad4 ASJ

AF:

0.668

Gnomad4 EAS

AF:

0.376

Gnomad4 SAS

AF:

0.626

Gnomad4 FIN

AF:

0.582

Gnomad4 NFE

AF:

0.629

Gnomad4 OTH

AF:

0.666

Alfa

AF:

0.636

Hom.:

5794

Bravo

AF:

0.643

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Isolated growth hormone deficiency, type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.6

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over