dbSNP rs1193745360: NBL1:p.Pro163Ala (chr1-19657070-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005380.8(NBL1):c.487C>G(p.Pro163Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. P163S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 27)

Consequence

NBL1
NM_005380.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.753

Publications

2 publications found

Variant links:

Genes affected

NBL1 (HGNC:7650): (NBL1, DAN family BMP antagonist) This gene product is the founding member of the evolutionarily conserved CAN (Cerberus and DAN) family of proteins, which contain a domain resembling the CTCK (C-terminal cystine knot-like) motif found in a number of signaling molecules. These proteins are secreted, and act as BMP (bone morphogenetic protein) antagonists by binding to BMPs and preventing them from interacting with their receptors. They may thus play an important role during growth and development. Alternatively spliced transcript variants have been identified for this gene. Read-through transcripts between this locus and the upstream mitochondrial inner membrane organizing system 1 gene (GeneID 440574) have been observed. [provided by RefSeq, May 2013]

NBL1 links:

MICOS10-NBL1 (HGNC:48338): (MICOS10-NBL1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring chromosome 1 open reading frame 151 (GeneID 440574) and neuroblastoma suppressor of tumorigenicity 1 (GeneID 4681) genes on chromosome 1. The read-through transcripts produce at least two proteins, each of which share identity with proteins translated from the downstream neuroblastoma suppressor of tumorigenicity 1 locus. [provided by RefSeq, Feb 2011]

MICOS10-NBL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15185377).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005380.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NBL1	NM_005380.8	MANE Select	c.487C>G	p.Pro163Ala	missense	Exon 4 of 4	NP_005371.2	P41271-1
NBL1	NM_182744.4		c.592C>G	p.Pro198Ala	missense	Exon 4 of 4	NP_877421.2	P41271-2
NBL1	NM_001204086.3		c.589C>G	p.Pro197Ala	missense	Exon 4 of 4	NP_001191015.1	A0A087WTY6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NBL1	ENST00000375136.8	TSL:1 MANE Select	c.487C>G	p.Pro163Ala	missense	Exon 4 of 4	ENSP00000364278.4	P41271-1
NBL1	ENST00000615215.4	TSL:1	c.589C>G	p.Pro197Ala	missense	Exon 4 of 4	ENSP00000478223.1	A0A087WTY6
NBL1	ENST00000618761.4	TSL:1	c.487C>G	p.Pro163Ala	missense	Exon 4 of 4	ENSP00000483061.1	P41271-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000696

AC:

AN:

143776

AF XY:

0.0000129

show subpopulations

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:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.19

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.18

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.79

M_CAP

Benign

0.0098

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.75

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.91

REVEL

Benign

0.021

Sift

Benign

0.14

Sift4G

Benign

0.53

Polyphen

0.073

Vest4

0.15

MVP

0.43

MPC

0.45

ClinPred

0.087

GERP RS

3.0

Varity_R

0.022

gMVP

0.082

Mutation Taster

=80/20

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over