3-173604665-CGG-GGA

Variant names:

• chr3-173604665-CGG-GGA
• NM_001365925.2:c.67_69delCGGinsGGA
• NLGN1 p.Arg23Gly

Variant summary

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

The NM_001365925.2(NLGN1):​c.67_69delCGGinsGGA​(p.Arg23Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. R23W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NLGN1 NM_001365925.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

Genes affected

NLGN1 (HGNC:14291): (neuroligin 1) 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. [provided by RefSeq, Jul 2008]

NLGN1 Gene-Disease associations (from GenCC):

• autism, susceptibility to, 20

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365925.2. 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
	NLGN1	NM_001365925.2	MANE Select	c.67_69delCGGinsGGA	p.Arg23Gly	missense	N/A	NP_001352854.1	A0A8Q3SHM6
	NLGN1	NM_001365923.2		c.67_69delCGGinsGGA	p.Arg23Gly	missense	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.67_69delCGGinsGGA	p.Arg23Gly	missense	N/A	NP_001352853.1	A0A8Q3SHM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	ENST00000695368.1	MANE Select	c.67_69delCGGinsGGA	p.Arg23Gly	missense	N/A	ENSP00000511841.1	A0A8Q3SHM6
	NLGN1	ENST00000415045.2	TSL:1	c.67_69delCGGinsGGA	p.Arg23Gly	missense	N/A	ENSP00000410374.2	C9J4D3
	NLGN1	ENST00000361589.8	TSL:1	c.67_69delCGGinsGGA	p.Arg23Gly	missense	N/A	ENSP00000354541.4	Q8N2Q7-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-173322455;