Variant chr17-3818302-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001114118.3(NCBP3):c.1271T>C(p.Met424Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NCBP3
NM_001114118.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.37

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NCBP3	NM_001114118.3 linkuse as main transcript	c.1271T>C	p.Met424Thr	missense_variant	10/13	ENST00000389005.6
NCBP3	NM_001398494.1 linkuse as main transcript	c.1271T>C	p.Met424Thr	missense_variant	10/14
NCBP3	XR_007065313.1 linkuse as main transcript	n.1294T>C		non_coding_transcript_exon_variant	10/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCBP3	ENST00000389005.6 linkuse as main transcript	c.1271T>C	p.Met424Thr	missense_variant	10/13	5	NM_001114118.3	P1	Q53F19-1
NCBP3	ENST00000574911.5 linkuse as main transcript	c.*479T>C		3_prime_UTR_variant, NMD_transcript_variant	5/8	1
NCBP3	ENST00000574379.2 linkuse as main transcript	n.879T>C		non_coding_transcript_exon_variant	3/3	2
NCBP3	ENST00000575815.5 linkuse as main transcript	n.1988T>C		non_coding_transcript_exon_variant	7/10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461120

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726766

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 23, 2024

The c.1271T>C (p.M424T) alteration is located in exon 10 (coding exon 10) of the NCBP3 gene. This alteration results from a T to C substitution at nucleotide position 1271, causing the methionine (M) at amino acid position 424 to be replaced by a threonine (T). 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

1.0

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.57

MutationTaster

Benign

1.0

D;D

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

Sift4G

Benign

0.28

Polyphen

0.97

Vest4

0.97

MutPred

0.26

Loss of sheet (P = 0.0126);

MVP

0.26

MPC

1.6

ClinPred

0.95

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.80

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