NM_001365588.1:c.260G>A

Variant names:

• chrY-14622379-G-A
• rs1556057385
• NM_001365588.1:c.260G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001365588.1(NLGN4Y):​c.260G>A​(p.Arg87Gln) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R87W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000028 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: NLGN4Y NM_001365588.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4Y	NM_001365588.1	MANE Select	c.260G>A	p.Arg87Gln	missense	Exon 2 of 7	NP_001352517.1	B4DHI3
	NLGN4Y	NM_001365584.1		c.260G>A	p.Arg87Gln	missense	Exon 2 of 7	NP_001352513.1	B4DHI3
	NLGN4Y	NM_001365586.1		c.260G>A	p.Arg87Gln	missense	Exon 2 of 7	NP_001352515.1	B4DHI3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4Y	ENST00000684976.1	MANE Select	c.260G>A	p.Arg87Gln	missense	Exon 2 of 7	ENSP00000510011.1	B4DHI3
	NLGN4Y	ENST00000382868.5	TSL:1	c.260G>A	p.Arg87Gln	missense	Exon 2 of 8	ENSP00000372320.1	A6NMU8
	NLGN4Y	ENST00000339174.9	TSL:1	c.260G>A	p.Arg87Gln	missense	Exon 2 of 6	ENSP00000342535.5	Q8NFZ3-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000275 AC: 1 AN: 363479 Hom.: 0 Cov.: 3 AF XY: 0.00000275 AC XY: 1 AN XY: 363479

African (AFR) AF: 0.00 AC: 0 AN: 7075

American (AMR) AF: 0.00 AC: 0 AN: 9507

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6747

East Asian (EAS) AF: 0.00 AC: 0 AN: 9494

South Asian (SAS) AF: 0.00 AC: 0 AN: 32106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12881

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1631

European-Non Finnish (NFE) AF: 0.00000371 AC: 1 AN: 269744

Other (OTH) AF: 0.00 AC: 0 AN: 14294

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.74	D
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.83	D
MutationAssessor	Pathogenic	4.3	H
PhyloP100		7.9
PROVEAN	Uncertain	-3.5	D
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.85
MVP		0.82
MPC		1.5
ClinPred		0.99	D
GERP RS		1.6
PromoterAI		0.0094	Neutral
Varity_R		0.64
Mutation Taster		=74/26	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1556057385; hg19: chrY-16734259; COSMIC: COSV52969676; COSMIC: COSV52969676;