chr1-146128149-G-T

Position:

• chr1-146128149-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001302371.3(NBPF10):​c.1771C>A​(p.Gln591Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 8)
• Consequence: NBPF10 NM_001302371.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.369

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 1-146128149-G-T is Benign according to our data. Variant chr1-146128149-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639089.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF10	NM_001302371.3	c.1771C>A	p.Gln591Lys	missense_variant	12/90	ENST00000583866.9
NBPF10	NM_001039703.6	c.1771C>A	p.Gln591Lys	missense_variant	12/86

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF10	ENST00000583866.9	c.1771C>A	p.Gln591Lys	missense_variant	12/90	5	NM_001302371.3	P1
NBPF10	ENST00000612520.2	c.1771C>A	p.Gln591Lys	missense_variant	17/21	5
NBPF10	ENST00000617010.2	c.-6105C>A		5_prime_UTR_variant	12/91	5

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Cov.: 11

GnomAD4 genome Cov.: 8

Alfa AF: 0.000223 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

NBPF10: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.0
DANN	Benign	0.63
Eigen	Benign	-0.79
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.099	T
Sift4G	Uncertain	0.011	D
Vest4		0.13
MVP		0.16
ClinPred		0.10	T
GERP RS		-0.54
gMVP		0.072

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.55		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: -2
DS_DL_spliceai		0.55		Position offset: 32

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs782751843; hg19: chr1-146234414;