rs587678061

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-146069571-C-A
• chr1-146069571-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 5/7 in silico tools predict 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

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.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBPF10	NM_001302371.3	c.10782G>T	p.Gln3594His	missense_variant	Exon 86 of 90	ENST00000583866.9	NP_001289300.1
NBPF10	NM_001039703.6	c.10275G>T	p.Gln3425His	missense_variant	Exon 82 of 86		NP_001034792.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBPF10	ENST00000583866.9	c.10782G>T	p.Gln3594His	missense_variant	Exon 86 of 90	5	NM_001302371.3	ENSP00000463957.6
NBPF10	ENST00000617010.2	c.3114G>T	p.Gln1038His	missense_variant	Exon 87 of 91	5		ENSP00000479344.2

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD3 exomes AF: 0.00000825 AC: 2 AN: 242416 Hom.: 0 AF XY: 0.00000759 AC XY: 1 AN XY: 131798

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 SAS exome AF: 0.0000332

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 18

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.5
DANN	Uncertain	0.98
LIST_S2	Uncertain	0.89	D;D
MetaRNN	Benign	0.10	T;T
Sift4G	Pathogenic	0.0	D;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

Publications

LitVar

Other links and lift over

dbSNP: rs587678061; hg19: chr1-145365431;