chrX-5892974-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_181332.3(NLGN4X):c.2294G>A(p.Arg765His) variant causes a missense change. The variant allele was found at a frequency of 0.0000141 in 1,209,347 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. R765R) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 21)
Exomes 𝑓: 0.000015 ( 0 hom. 4 hem. )
Consequence
NLGN4X
NM_181332.3 missense
NM_181332.3 missense
Scores
2
9
5
Clinical Significance
Conservation
PhyloP100: 6.80
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NLGN4X | NM_181332.3 | c.2294G>A | p.Arg765His | missense_variant | 6/6 | ENST00000381095.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLGN4X | ENST00000381095.8 | c.2294G>A | p.Arg765His | missense_variant | 6/6 | 1 | NM_181332.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000900 AC: 1AN: 111079Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 33279
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GnomAD3 exomes AF: 0.00000545 AC: 1AN: 183525Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67953
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GnomAD4 exome AF: 0.0000146 AC: 16AN: 1098268Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 4AN XY: 363622
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autism, susceptibility to, X-linked 2 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Institute of Human Genetics, University of Goettingen | Jul 23, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Uncertain
D;D;D;.;D
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;.;D;.;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;.;D
Sift4G
Uncertain
D;D;D;.;D
Polyphen
D;D;D;D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at