NM_181303.2:c.229C>G

Variant names:

• chrX-71147978-C-G
• NM_181303.2:c.229C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181303.2(NLGN3):​c.229C>G​(p.Pro77Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: NLGN3 NM_181303.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.66

Genes affected

NLGN3 (HGNC:14289): (neuroligin 3) This gene encodes a member of a family of neuronal cell surface proteins. Members of this family may act as splice site-specific ligands for beta-neurexins and may be involved in the formation and remodeling of central nervous system synapses. Mutations in this gene may be associated with autism and Asperger syndrome. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Oct 2009]

LOC124905197 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN3	NM_181303.2	c.229C>G	p.Pro77Ala	missense_variant	Exon 2 of 8	ENST00000358741.4	NP_851820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN3	ENST00000358741.4	c.229C>G	p.Pro77Ala	missense_variant	Exon 2 of 8	5	NM_181303.2	ENSP00000351591.4
NLGN3	ENST00000685718.1	n.229C>G		non_coding_transcript_exon_variant	Exon 2 of 8			ENSP00000510514.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.69	.;.;.;D
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.0	L;.;L;L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.4	D;D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.15	T;T;T;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.013	.;.;B;.
Vest4		0.54
MutPred		0.85		Loss of disorder (P = 0.054);Loss of disorder (P = 0.054);Loss of disorder (P = 0.054);Loss of disorder (P = 0.054);
MVP		0.75
MPC		1.4
ClinPred		0.40	T
GERP RS		3.9
Varity_R		0.24
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-70367828;