rs5916352

Variant names:

• chrX-6224327-C-G
• rs5916352
• NM_181332.3:c.-306+4214G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-6224327-C-G
• chrX-6224327-C-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.-306+4214G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 110,468 control chromosomes in the GnomAD database, including 8,673 homozygotes. There are 13,706 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 0.43 (8673 hom., 13706 hem., cov: 22)
• Consequence: NLGN4X NM_181332.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• Publications: 2 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4X	NM_181332.3	MANE Select	c.-306+4214G>C		intron	N/A	NP_851849.1	Q8N0W4-1
	NLGN4X	NM_001282145.2		c.-613+4214G>C		intron	N/A	NP_001269074.1	Q8N0W4-1
	NLGN4X	NM_001282146.2		c.-306+2553G>C		intron	N/A	NP_001269075.1	Q8N0W4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4X	ENST00000381095.8	TSL:1 MANE Select	c.-306+4214G>C		intron	N/A	ENSP00000370485.3	Q8N0W4-1
	NLGN4X	ENST00000275857.10	TSL:1	c.-306+3362G>C		intron	N/A	ENSP00000275857.6	Q8N0W4-1
	NLGN4X	ENST00000381092.1	TSL:2	c.-613+4214G>C		intron	N/A	ENSP00000370482.1	Q8N0W4-1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 47847 AN: 110417 Hom.: 8666 Cov.: 22

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.434 AC: 47901 AN: 110468 Hom.: 8673 Cov.: 22 AF XY: 0.419 AC XY: 13706 AN XY: 32746

African (AFR) AF: 0.693 AC: 20987 AN: 30282

American (AMR) AF: 0.355 AC: 3707 AN: 10443

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 752 AN: 2634

East Asian (EAS) AF: 0.177 AC: 618 AN: 3489

South Asian (SAS) AF: 0.283 AC: 748 AN: 2646

European-Finnish (FIN) AF: 0.370 AC: 2151 AN: 5811

Middle Eastern (MID) AF: 0.404 AC: 86 AN: 213

European-Non Finnish (NFE) AF: 0.340 AC: 17939 AN: 52772

Other (OTH) AF: 0.410 AC: 618 AN: 1506

Alfa AF: 0.379 Hom.: 2485

Bravo AF: 0.449

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.63
PhyloP100		0.49
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

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

Other links and lift over

dbSNP: rs5916352;

hg19: chrX-6142368;