Variant 17-3821333-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001114118.3(NCBP3):c.916C>T(p.Arg306Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

NCBP3
NM_001114118.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17

Variant links:

Genes affected

NCBP3 (HGNC:24612): (nuclear cap binding subunit 3) Enables RNA 7-methylguanosine cap binding activity and mRNA binding activity. Involved in defense response to virus. Located in cytoplasm and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

NCBP3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4175862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NCBP3	NM_001114118.3 linkuse as main transcript	c.916C>T	p.Arg306Cys	missense_variant	9/13	ENST00000389005.6
NCBP3	NM_001398494.1 linkuse as main transcript	c.916C>T	p.Arg306Cys	missense_variant	9/14
NCBP3	XR_007065313.1 linkuse as main transcript	n.939C>T		non_coding_transcript_exon_variant	9/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCBP3	ENST00000389005.6 linkuse as main transcript	c.916C>T	p.Arg306Cys	missense_variant	9/13	5	NM_001114118.3	P1	Q53F19-1
NCBP3	ENST00000574911.5 linkuse as main transcript	c.*124C>T		3_prime_UTR_variant, NMD_transcript_variant	4/8	1
NCBP3	ENST00000574379.2 linkuse as main transcript	n.524C>T		non_coding_transcript_exon_variant	2/3	2
NCBP3	ENST00000575815.5 linkuse as main transcript	n.1633C>T		non_coding_transcript_exon_variant	6/10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461596

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727084

show subpopulations

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 19, 2022

The c.916C>T (p.R306C) alteration is located in exon 9 (coding exon 9) of the NCBP3 gene. This alteration results from a C to T substitution at nucleotide position 916, causing the arginine (R) at amino acid position 306 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.096

Eigen

Benign

0.082

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.016

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.78

MutationTaster

Benign

1.0

D;D

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.013

Polyphen

0.0030

Vest4

0.85

MutPred

0.34

Loss of disorder (P = 0.0237);

MVP

0.068

MPC

1.9

ClinPred

0.99

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.46

gMVP

0.67

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