Genetic Variant NLGN4Y:p.Asn421Lys (chrY-14830121-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: YL Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

NLGN4Y links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365588.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLGN4Y	NM_001365588.1	MANE Select	c.1263C>A	p.Asn421Lys	missense	Exon 6 of 7	NP_001352517.1	B4DHI3
NLGN4Y	NM_001365584.1		c.1263C>A	p.Asn421Lys	missense	Exon 6 of 7	NP_001352513.1	B4DHI3
NLGN4Y	NM_001365586.1		c.1263C>A	p.Asn421Lys	missense	Exon 6 of 7	NP_001352515.1	B4DHI3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLGN4Y	ENST00000684976.1	MANE Select	c.1263C>A	p.Asn421Lys	missense	Exon 6 of 7	ENSP00000510011.1	B4DHI3
NLGN4Y	ENST00000382868.5	TSL:1	c.1374C>A	p.Asn458Lys	missense	Exon 7 of 8	ENSP00000372320.1	A6NMU8
NLGN4Y	ENST00000339174.9	TSL:1	c.1203C>A	p.Asn401Lys	missense	Exon 5 of 6	ENSP00000342535.5	Q8NFZ3-1

Frequencies

GnomAD3 genomes

AF:

0.0000625

AC:

AN:

32010

Hom.:

Cov.:

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

African (AFR)

AF:

0.00

AC:

AN:

7009

American (AMR)

AF:

0.00

AC:

AN:

9386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6699

East Asian (EAS)

AF:

0.00

AC:

AN:

9451

South Asian (SAS)

AF:

0.00

AC:

AN:

31926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1609

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

266352

Other (OTH)

AF:

0.00

AC:

AN:

14136

Age Distribution

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

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

African (AFR)

AF:

0.00

AC:

AN:

8049

American (AMR)

AF:

0.00

AC:

AN:

3594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

755

East Asian (EAS)

AF:

0.00

AC:

AN:

1206

South Asian (SAS)

AF:

0.00

AC:

AN:

1367

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3243

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000153

AC:

AN:

13088

Other (OTH)

AF:

0.00

AC:

AN:

428

Age Distribution

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

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

FATHMM_MKL

Benign

0.66

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.24

MutationAssessor

Benign

-0.045

PhyloP100

3.6

PROVEAN

Uncertain

-3.0

Sift

Benign

0.10

Sift4G

Benign

0.45

Polyphen

0.73

Vest4

0.49

MVP

0.10

MPC

0.71

GERP RS

1.7

Varity_R

0.50

Mutation Taster

=80/20

polymorphism

(source)

Splicing

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