Genetic Variant NBPF10:p.Gln3594Gln (chr1-146069571-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001302371.3(NBPF10):c.10782G>A(p.Gln3594Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,239,820 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 18)

Exomes 𝑓: 0.00011 ( 4 hom. )

Consequence

NBPF10
NM_001302371.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.149

Variant links:

Genes affected

NBPF10 (HGNC:31992): (NBPF member 10) 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 results in multiple transcript variants. [provided by RefSeq, Oct 2014]

NBPF10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-146069571-C-T is Benign according to our data. Variant chr1-146069571-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639104.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.149 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBPF10	NM_001302371.3 link	c.10782G>A	p.Gln3594Gln	synonymous_variant	Exon 86 of 90	ENST00000583866.9	NP_001289300.1	Q6P3W6
NBPF10	NM_001039703.6 link	c.10275G>A	p.Gln3425Gln	synonymous_variant	Exon 82 of 86		NP_001034792.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBPF10	ENST00000583866.9 link	c.10782G>A	p.Gln3594Gln	synonymous_variant	Exon 86 of 90	5	NM_001302371.3	ENSP00000463957.6		Q6P3W6
NBPF10	ENST00000617010.2 link	c.3114G>A	p.Gln1038Gln	synonymous_variant	Exon 87 of 91	5		ENSP00000479344.2		A0A087WVC7

Frequencies

GnomAD3 genomes

AF:

0.0000918

AC:

AN:

108976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000972

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000269

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000114

Gnomad OTH

AF:

0.000687

GnomAD3 exomes

AF:

0.000177

AC:

AN:

242416

Hom.:

AF XY:

0.000152

AC XY:

AN XY:

131798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000665

Gnomad FIN exome

AF:

0.000280

Gnomad NFE exome

AF:

0.000284

Gnomad OTH exome

AF:

0.000510

GnomAD4 exome

AF:

0.000111

AC:

125

AN:

1130806

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

574268

show subpopulations

Gnomad4 AFR exome

AF:

0.0000419

Gnomad4 AMR exome

AF:

0.0000243

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.000182

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.0000411

GnomAD4 genome

AF:

0.0000917

AC:

AN:

109014

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

53026

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000971

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000269

Gnomad4 NFE

AF:

0.000114

Gnomad4 OTH

AF:

0.000679

Alfa

AF:

0.000145

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NBPF10: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.37

DANN

Benign

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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