rs1841532542

Variant names:

• chr10-81875450-G-A
• rs1841532542
• NM_001010848.4:c.110G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-81875450-G-A
• chr10-81875450-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010848.4(NRG3):​c.110G>A​(p.Gly37Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,072,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G37V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: NRG3 NM_001010848.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 0 publications found

Genes affected

NRG3 (HGNC:7999): (neuregulin 3) This gene is a member of the neuregulin gene family. This gene family encodes ligands for the transmembrane tyrosine kinase receptors ERBB3 and ERBB4 - members of the epidermal growth factor receptor family. Ligand binding activates intracellular signaling cascades and the induction of cellular responses including proliferation, migration, differentiation, and survival or apoptosis. This gene encodes neuregulin 3 (NRG3). NRG3 has been shown to activate the tyrosine phosphorylation of its cognate receptor, ERBB4, and is thought to influence neuroblast proliferation, migration and differentiation by signalling through ERBB4. NRG3 also promotes mammary differentiation during embryogenesis. Linkage studies have implicated this gene as a susceptibility locus for schizophrenia and schizoaffective disorder. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described but their biological validity has not been verified.[provided by RefSeq, Sep 2009]

ENSG00000287358 (HGNC:):

ACMG classification

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=0.08964962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRG3	NM_001010848.4	c.110G>A	p.Gly37Asp	missense_variant	Exon 1 of 9	ENST00000372141.7	NP_001010848.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRG3	ENST00000372141.7	c.110G>A	p.Gly37Asp	missense_variant	Exon 1 of 9	1	NM_001010848.4	ENSP00000361214.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000187 AC: 2 AN: 1072050 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 507370

African (AFR) AF: 0.00 AC: 0 AN: 22486

American (AMR) AF: 0.00 AC: 0 AN: 8670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13696

East Asian (EAS) AF: 0.00 AC: 0 AN: 25474

South Asian (SAS) AF: 0.00 AC: 0 AN: 20024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3396

European-Non Finnish (NFE) AF: 0.00000219 AC: 2 AN: 913786

Other (OTH) AF: 0.00 AC: 0 AN: 42766

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.18	.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.090	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		1.7
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.097
Sift	Uncertain	0.012	D;D
Sift4G	Benign	0.39	T;T
Polyphen		0.20	B;.
Vest4		0.24
MutPred		0.12		Gain of solvent accessibility (P = 0.2291);Gain of solvent accessibility (P = 0.2291);
MVP		0.27
MPC		0.73
ClinPred		0.14	T
GERP RS		1.1
PromoterAI		0.012	Neutral
Varity_R		0.12
gMVP		0.15
Mutation Taster		=88/12	polymorphism

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: rs1841532542; hg19: chr10-83635206;