Variant chr1-108465355-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001143988.2(NBPF6):c.1591C>T(p.Arg531Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 11)

Exomes 𝑓: 0.000024 ( 6 hom. )

Consequence

NBPF6
NM_001143988.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00600

Variant links:

Genes affected

NBPF6 (HGNC:31988): (NBPF member 6) 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. Gene copy number variations in the 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. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2013]

NBPF6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.117302835).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF6	NM_001143988.2 linkuse as main transcript	c.1591C>T	p.Arg531Trp	missense_variant	13/15	ENST00000495380.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF6	ENST00000495380.7 linkuse as main transcript	c.1591C>T	p.Arg531Trp	missense_variant	13/15	5	NM_001143988.2		Q5VWK0-1
NBPF6	ENST00000531446.2 linkuse as main transcript	c.1678C>T	p.Arg560Trp	missense_variant	14/14	1
NBPF6	ENST00000370040.7 linkuse as main transcript	c.1678C>T	p.Arg560Trp	missense_variant	14/16	5		P1	Q5VWK0-2

Frequencies

GnomAD3 genomes

AF:

0.0000230

AC:

AN:

86946

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:

0.000364

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000238

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000464

AC:

AN:

107814

Hom.:

AF XY:

0.0000344

AC XY:

AN XY:

58096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000545

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000514

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000244

AC:

AN:

984392

Hom.:

Cov.:

AF XY:

0.0000326

AC XY:

AN XY:

491216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000958

Gnomad4 AMR exome

AF:

0.0000679

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000357

Gnomad4 SAS exome

AF:

0.0000307

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000230

AC:

AN:

86946

Hom.:

Cov.:

AF XY:

0.0000240

AC XY:

AN XY:

41604

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:

0.000364

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000238

Gnomad4 OTH

AF:

0.00

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

Feb 28, 2023

The c.1678C>T (p.R560W) alteration is located in exon 14 (coding exon 13) of the NBPF6 gene. This alteration results from a C to T substitution at nucleotide position 1678, causing the arginine (R) at amino acid position 560 to be replaced by a tryptophan (W). 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

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.88

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.087

Sift

Uncertain

0.026

D;D;D

Sift4G

Uncertain

0.022

D;D;D

Polyphen

0.99

.;D;.

Vest4

0.16

MutPred

0.38

.;Loss of disorder (P = 0.0061);.;

MVP

0.32

ClinPred

0.079

GERP RS

-0.054

Varity_R

0.045

gMVP

0.0064

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