Variant rs1057524272 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001365588.1(NLGN4Y):c.1263C>A(p.Asn421Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 2 hem., cov: 0)

Exomes 𝑓: 0.000014 ( 0 hom. 5 hem. )

Failed GnomAD Quality Control

Consequence

NLGN4Y
NM_001365588.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

Variant links:

Genes affected

NLGN4Y (HGNC:15529): (neuroligin 4 Y-linked) This gene encodes a type I membrane protein that belongs to the family of neuroligins, which are cell adhesion molecules present at the postsynaptic side of the synapse, and may be essential for the formation of functional synapses. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Mar 2011]

NLGN4Y links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.239351).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4Y	NM_001365588.1 link	c.1263C>A	p.Asn421Lys	missense_variant	Exon 6 of 7	ENST00000684976.1	NP_001352517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN4Y	ENST00000684976.1 link	c.1263C>A	p.Asn421Lys	missense_variant	Exon 6 of 7		NM_001365588.1	ENSP00000510011.1		B4DHI3

Frequencies

GnomAD3 genomes

AF:

0.0000625

AC:

AN:

32010

Hom.:

Cov.:

AF XY:

0.0000625

AC XY:

AN XY:

32010

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000153

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000139

AC:

AN:

359358

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

359358

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000188

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000625

AC:

AN:

32010

Hom.:

Cov.:

AF XY:

0.0000625

AC XY:

AN XY:

32010

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000153

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jan 06, 2017

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The N401K variant in the NLGN4Y gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N401K variant was not observed in the Exome Aggregation Consortium (ExAC) data set, indicating it is not a common benign variant (Lek et al., 2016). The N401K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret N401K as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

.;.;T;.;T

FATHMM_MKL

Benign

0.66

LIST_S2

Pathogenic

0.98

D;D;.;D;D

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.24

T;T;T;T;T

MutationAssessor

Benign

-0.045

.;.;N;.;N

PROVEAN

Uncertain

-3.0

.;D;D;D;D

Sift

Benign

0.10

.;T;T;T;T

Sift4G

Benign

0.45

.;T;T;T;T

Polyphen

0.73

P;.;B;.;B

Vest4

0.49, 0.49, 0.49, 0.49

MVP

0.10

MPC

0.71

GERP RS

1.7

Varity_R

0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over