Genetic Variant NM_181332.3:c.*284G>T (chrX-5892533-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_181332.3(NLGN4X):c.*284G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 331,497 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 96 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 0.00083 ( 0 hom., 22 hem., cov: 23)

Exomes 𝑓: 0.0012 ( 0 hom. 74 hem. )

Consequence

NLGN4X
NM_181332.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00700

Publications

7 publications found

Variant links:

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

NLGN4X links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BS2

High Hemizygotes in GnomAd4 at 22 XL gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NLGN4X	NM_181332.3	MANE Select	c.*284G>T	3_prime_UTR	Exon 6 of 6	NP_851849.1
NLGN4X	NM_001282145.2		c.*284G>T	3_prime_UTR	Exon 7 of 7	NP_001269074.1
NLGN4X	NM_001282146.2		c.*284G>T	3_prime_UTR	Exon 6 of 6	NP_001269075.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NLGN4X	ENST00000381095.8	TSL:1 MANE Select	c.*284G>T	3_prime_UTR	Exon 6 of 6	ENSP00000370485.3
NLGN4X	ENST00000538097.6	TSL:1	c.*284G>T	3_prime_UTR	Exon 6 of 6	ENSP00000439203.3
NLGN4X	ENST00000275857.10	TSL:1	c.*284G>T	3_prime_UTR	Exon 6 of 6	ENSP00000275857.6

Frequencies

GnomAD3 genomes

AF:

0.000829

AC:

AN:

110960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000171

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.000668

GnomAD4 exome

AF:

0.00118

AC:

261

AN:

220481

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

65619

show subpopulations

African (AFR)

AF:

0.000414

AC:

AN:

7248

American (AMR)

AF:

0.000183

AC:

AN:

10955

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6437

East Asian (EAS)

AF:

0.00

AC:

AN:

13477

South Asian (SAS)

AF:

0.00205

AC:

AN:

22406

European-Finnish (FIN)

AF:

0.000518

AC:

AN:

11580

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

887

European-Non Finnish (NFE)

AF:

0.00141

AC:

189

AN:

134417

Other (OTH)

AF:

0.000994

AC:

AN:

13074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000829

AC:

AN:

111016

Hom.:

Cov.:

AF XY:

0.000662

AC XY:

AN XY:

33240

show subpopulations

African (AFR)

AF:

0.000130

AC:

AN:

30687

American (AMR)

AF:

0.000191

AC:

AN:

10472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3498

South Asian (SAS)

AF:

0.00

AC:

AN:

2600

European-Finnish (FIN)

AF:

0.000171

AC:

AN:

5843

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00159

AC:

AN:

52867

Other (OTH)

AF:

0.000660

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00000285

Hom.:

45347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.20

(source)

DANN

Benign

0.51

PhyloP100

-0.0070

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over