1-21445184-G-T

Position:

chr1-21445184-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330381.3(NBPF3):c.-472G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,768 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

NBPF3
NM_001330381.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.211

Variant links:

Genes affected

NBPF3 (HGNC:25076): (NBPF member 3) This gene is a member of the neuroblastoma breakpoint family (NBPF) which consists of dozens of recently duplicated genes primarily located in segmental duplications on human chromosome 1. This gene family has experienced its greatest expansion within the human lineage and has expanded, to a lesser extent, among primates in general. Members of this gene family are characterized by tandemly repeated copies of DUF1220 protein domains. DUF1220 copy number variations in human chromosomal region 1q21.1, where most DUF1220 domains are located, have been implicated in a number of developmental and neurogenetic diseases such as microcephaly, macrocephaly, autism, schizophrenia, cognitive disability, congenital heart disease, neuroblastoma, and congenital kidney and urinary tract anomalies. Altered expression of some gene family members is associated with several types of cancer. This gene family contains numerous pseudogenes. [provided by RefSeq, Feb 2013]

NBPF3 links:

NBPF3 (HGNC:):

NBPF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.088046044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBPF3	NM_032264.6 linkuse as main transcript	c.98G>T	p.Gly33Val	missense_variant	2/15	ENST00000318249.10	NP_115640.1	Q9H094-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NBPF3	ENST00000318249.10 linkuse as main transcript	c.98G>T	p.Gly33Val	missense_variant	2/15	1	NM_032264.6	ENSP00000316782.5	Q9H094-1
NBPF3	ENST00000434838.6 linkuse as main transcript	n.98G>T		non_coding_transcript_exon_variant	1/19	5		ENSP00000391865.2	X6RCV0
NBPF3	ENST00000467103.2 linkuse as main transcript	n.98G>T		non_coding_transcript_exon_variant	1/3	5		ENSP00000479028.1	A0A087WUY9

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250938

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1459678

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726140

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

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

Mar 30, 2024

The c.98G>T (p.G33V) alteration is located in exon 2 (coding exon 1) of the NBPF3 gene. This alteration results from a G to T substitution at nucleotide position 98, causing the glycine (G) at amino acid position 33 to be replaced by a valine (V). 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

Benign

0.16

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.8

DANN

Benign

0.91

DEOGEN2

Benign

0.0019

.;.;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.46

T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.088

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

1.2

N;N;N

REVEL

Benign

0.026

Sift

Benign

0.15

T;D;D

Sift4G

Uncertain

0.041

D;D;D

Polyphen

0.99, 0.23

.;D;B

Vest4

0.20

MutPred

0.12

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

0.16

MPC

0.56

ClinPred

0.17

GERP RS

0.13

Varity_R

0.084

gMVP

0.048

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