X-5937979-G-A

Variant names:

• chrX-5937979-G-A
• rs6529901
• NM_181332.3:c.626-28740C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181332.3(NLGN4X):​c.626-28740C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 110,804 control chromosomes in the GnomAD database, including 4,465 homozygotes. There are 10,036 hemizygotes in GnomAD. 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 0.30 (4465 hom., 10036 hem., cov: 23)
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 4 publications found

Genes affected

NLGN4X (HGNC:14287): (neuroligin 4 X-linked) This gene encodes a member of the type-B carboxylesterase/lipase protein family. The encoded protein belongs to 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. The encoded protein interacts with discs large homolog 4 (DLG4). Mutations in this gene have been associated with autism and Asperger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

NLGN4X Gene-Disease associations (from GenCC):

• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• autism, susceptibility to, X-linked 2

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181332.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4X	NM_181332.3	MANE Select	c.626-28740C>T		intron	N/A	NP_851849.1
	NLGN4X	NM_001282145.2		c.626-28740C>T		intron	N/A	NP_001269074.1
	NLGN4X	NM_001282146.2		c.626-28740C>T		intron	N/A	NP_001269075.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4X	ENST00000381095.8	TSL:1 MANE Select	c.626-28740C>T		intron	N/A	ENSP00000370485.3
	NLGN4X	ENST00000538097.6	TSL:1	c.686-28740C>T		intron	N/A	ENSP00000439203.3
	NLGN4X	ENST00000275857.10	TSL:1	c.626-28740C>T		intron	N/A	ENSP00000275857.6

Frequencies

GnomAD3 genomes AF: 0.301 AC: 33310 AN: 110754 Hom.: 4468 Cov.: 23

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.552

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.301 AC: 33303 AN: 110804 Hom.: 4465 Cov.: 23 AF XY: 0.304 AC XY: 10036 AN XY: 33056

African (AFR) AF: 0.0601 AC: 1845 AN: 30715

American (AMR) AF: 0.328 AC: 3423 AN: 10443

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1106 AN: 2622

East Asian (EAS) AF: 0.579 AC: 1991 AN: 3438

South Asian (SAS) AF: 0.454 AC: 1194 AN: 2631

European-Finnish (FIN) AF: 0.429 AC: 2487 AN: 5793

Middle Eastern (MID) AF: 0.565 AC: 118 AN: 209

European-Non Finnish (NFE) AF: 0.390 AC: 20552 AN: 52762

Other (OTH) AF: 0.315 AC: 477 AN: 1514

Alfa AF: 0.333 Hom.: 2873

Bravo AF: 0.286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.41
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs6529901; hg19: chrX-5856020;