Variant 1-103533873-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017619.4(RNPC3):c.359+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,192,612 control chromosomes in the GnomAD database, including 228,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 35413 hom., cov: 29)

Exomes 𝑓: 0.60 ( 193066 hom. )

Consequence

RNPC3
NM_017619.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.937

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-103533873-A-G is Benign according to our data. Variant chr1-103533873-A-G is described in ClinVar as [Benign]. Clinvar id is 1327963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 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.359+16A>G		intron_variant		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.359+16A>G		intron_variant		1	NM_017619.4	ENSP00000391432	P4	Q96LT9-1

Frequencies

GnomAD3 genomes

AF:

0.673

AC:

101817

AN:

151210

Hom.:

35380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.843

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.668

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.695

GnomAD3 exomes

AF:

0.621

AC:

83678

AN:

134736

Hom.:

26677

AF XY:

0.624

AC XY:

45169

AN XY:

72432

show subpopulations

Gnomad AFR exome

AF:

0.854

Gnomad AMR exome

AF:

0.578

Gnomad ASJ exome

AF:

0.668

Gnomad EAS exome

AF:

0.375

Gnomad SAS exome

AF:

0.637

Gnomad FIN exome

AF:

0.592

Gnomad NFE exome

AF:

0.640

Gnomad OTH exome

AF:

0.638

GnomAD4 exome

AF:

0.604

AC:

629219

AN:

1041284

Hom.:

193066

Cov.:

AF XY:

0.606

AC XY:

320593

AN XY:

528886

show subpopulations

Gnomad4 AFR exome

AF:

0.846

Gnomad4 AMR exome

AF:

0.575

Gnomad4 ASJ exome

AF:

0.660

Gnomad4 EAS exome

AF:

0.339

Gnomad4 SAS exome

AF:

0.619

Gnomad4 FIN exome

AF:

0.586

Gnomad4 NFE exome

AF:

0.606

Gnomad4 OTH exome

AF:

0.623

GnomAD4 genome

AF:

0.673

AC:

101905

AN:

151328

Hom.:

35413

Cov.:

AF XY:

0.666

AC XY:

49297

AN XY:

73968

show subpopulations

Gnomad4 AFR

AF:

0.843

Gnomad4 AMR

AF:

0.610

Gnomad4 ASJ

AF:

0.668

Gnomad4 EAS

AF:

0.372

Gnomad4 SAS

AF:

0.629

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.628

Gnomad4 OTH

AF:

0.691

Alfa

AF:

0.650

Hom.:

5797

Bravo

AF:

0.683

Asia WGS

AF:

0.561

AC:

1951

AN:

3478

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

-0.84

CADD

Benign

3.2

DANN

Benign

0.69

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

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