1-146069571-C-A

Variant names:

• chr1-146069571-C-A
• rs587678061
• NM_001302371.3:c.10782G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001302371.3(NBPF10):​c.10782G>T​(p.Gln3594His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q3594Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF10 NM_001302371.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10299605).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302371.3. 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
	NBPF10	NM_001302371.3	MANE Select	c.10782G>T	p.Gln3594His	missense	Exon 86 of 90	NP_001289300.1	Q6P3W6
	NBPF10	NM_001039703.6		c.10275G>T	p.Gln3425His	missense	Exon 82 of 86	NP_001034792.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF10	ENST00000583866.9	TSL:5 MANE Select	c.10782G>T	p.Gln3594His	missense	Exon 86 of 90	ENSP00000463957.6	Q6P3W6

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD2 exomes AF: 0.00000825 AC: 2 AN: 242416 AF XY: 0.00000759

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000918

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.84e-7 AC: 1 AN: 1130862 Hom.: 0 Cov.: 27 AF XY: 0.00000174 AC XY: 1 AN XY: 574296

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23892

American (AMR) AF: 0.00 AC: 0 AN: 41090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23562

East Asian (EAS) AF: 0.00 AC: 0 AN: 37640

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3444

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 821888

Other (OTH) AF: 0.00 AC: 0 AN: 48612

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 18

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.5
DANN	Uncertain	0.98
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.10	T
PhyloP100		-0.15
Sift4G	Pathogenic	0.0	D
Vest4		0.17
gMVP		0.034

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs587678061; hg19: chr1-145365431;