3-173553894-C-T

Variant names:

• chr3-173553894-C-T
• rs9290474
• NM_001365925.2:c.-320-50385C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365925.2(NLGN1):​c.-320-50385C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.-320-50385C>T		intron_variant	Intron 1 of 6	ENST00000695368.1	NP_001352854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN1	ENST00000695368.1	c.-320-50385C>T		intron_variant	Intron 1 of 6		NM_001365925.2	ENSP00000511841.1
NLGN1	ENST00000457714.5	c.-320-50385C>T		intron_variant	Intron 2 of 6	1		ENSP00000392500.1
NLGN1	ENST00000423427.1	c.-320-50385C>T		intron_variant	Intron 1 of 1	4		ENSP00000407255.1
NLGN1	ENST00000413821.1	c.-320-50385C>T		intron_variant	Intron 1 of 1	4		ENSP00000401843.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151886 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151886 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74160

African (AFR) AF: 0.00 AC: 0 AN: 41374

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000949 AC: 1 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000161 Hom.: 7577

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.94
PhyloP100		-0.13

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: rs9290474; hg19: chr3-173271684;