3-173800306-GAAAC-G

Position:

• chr3-173800306-GAAAC-G

Variant summary

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

The ENST00000415045.2(NLGN1):​c.569_572del​(p.Lys190ArgfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000956 in 1,045,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.6e-7 (0 hom.)
• Consequence: NLGN1 ENST00000415045.2 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.90

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]

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/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.554-7372_554-7369del		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000415045.2	c.569_572del	p.Lys190ArgfsTer5	frameshift_variant	4/8	1
NLGN1	ENST00000695368.1	c.554-7372_554-7369del		intron_variant			NM_001365925.2	A1
NLGN1	ENST00000361589.8	c.494-7372_494-7369del		intron_variant		1		P2
NLGN1	ENST00000457714.5	c.494-7372_494-7369del		intron_variant		1		P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.56e-7 AC: 1 AN: 1045654 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 512706

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000116

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University Hospital Muenster

Oct 19, 2022

ACMG categories: PVS1 -

Computational scores

Source: dbNSFP v4.3

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: chr3-173518096;