chrX-5892947-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_181332.3(NLGN4X):c.2321T>C(p.Met774Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,209,544 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 (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 21)
Exomes 𝑓: 0.0000091 ( 0 hom. 4 hem. )
Consequence
NLGN4X
NM_181332.3 missense
NM_181332.3 missense
Scores
1
11
4
Clinical Significance
Conservation
PhyloP100: 8.00
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.2321T>C | p.Met774Thr | missense_variant | 6/6 | ENST00000381095.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NLGN4X | ENST00000381095.8 | c.2321T>C | p.Met774Thr | missense_variant | 6/6 | 1 | NM_181332.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000180 AC: 2AN: 111275Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 33467
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GnomAD3 exomes AF: 0.0000272 AC: 5AN: 183531Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67959
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GnomAD4 exome AF: 0.00000911 AC: 10AN: 1098269Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 4AN XY: 363623
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GnomAD4 genome ? AF: 0.0000180 AC: 2AN: 111275Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 33467
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 31, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
T;T;T;.;T
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
P;P;P;D;P
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