1-149063639-T-C

Variant names:

• chr1-149063639-T-C
• rs781909017
• NM_001388367.1:c.2020A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001388367.1(NBPF9):​c.2020A>G​(p.Met674Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M674L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 19)
• Consequence: NBPF9 NM_001388367.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 0 publications found

Genes affected

NBPF9 (HGNC:31991): (NBPF member 9) 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. [provided by RefSeq, Apr 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050377846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388367.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF9	NM_001388367.1	MANE Select	c.2020A>G	p.Met674Val	missense	Exon 20 of 30	NP_001375296.1	P0DPF3-1
	NBPF9	NM_001277444.2		c.2020A>G	p.Met674Val	missense	Exon 20 of 30	NP_001264373.1	P0DPF3-1
	NBPF9	NM_001388366.1		c.2020A>G	p.Met674Val	missense	Exon 21 of 31	NP_001375295.1	P0DPF3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF9	ENST00000698832.1	MANE Select	c.2020A>G	p.Met674Val	missense	Exon 20 of 30	ENSP00000513968.1	P0DPF3-1
	NBPF9	ENST00000610300.4	TSL:1	c.2020A>G	p.Met674Val	missense	Exon 15 of 21	ENSP00000481471.1	P0DPF3-2
	NBPF9	ENST00000613595.4	TSL:1	c.2020A>G	p.Met674Val	missense	Exon 15 of 21	ENSP00000483900.1	P0DPF3-2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.014
DANN	Benign	0.10
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.050	T
PhyloP100		-0.14
Sift4G	Benign	1.0	T
Vest4		0.099
PromoterAI		0.060	Neutral

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

Other links and lift over

dbSNP: rs781909017; hg19: chr1-144823979;