NM_001365588.1:c.685+4350G>A

Variant names:

• chrY-14727619-G-A
• rs17222279
• NM_001365588.1:c.685+4350G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001365588.1(NLGN4Y):​c.685+4350G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0056 (0 hom., 185 hem., cov: 0)
• Consequence: NLGN4Y NM_001365588.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 4 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Hemizygotes in GnomAd4 at 185 YL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN4Y	NM_001365588.1	c.685+4350G>A		intron_variant	Intron 4 of 6	ENST00000684976.1	NP_001352517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN4Y	ENST00000684976.1	c.685+4350G>A		intron_variant	Intron 4 of 6		NM_001365588.1	ENSP00000510011.1

Frequencies

GnomAD3 genomes AF: 0.00557 AC: 185 AN: 33215 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00505

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000297

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00984

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00556 AC: 185 AN: 33276 Hom.: 0 Cov.: 0 AF XY: 0.00556 AC XY: 185 AN XY: 33276

African (AFR) AF: 0.00502 AC: 43 AN: 8565

American (AMR) AF: 0.00222 AC: 8 AN: 3598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 761

East Asian (EAS) AF: 0.00 AC: 0 AN: 1288

South Asian (SAS) AF: 0.00 AC: 0 AN: 1447

European-Finnish (FIN) AF: 0.000297 AC: 1 AN: 3370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 71

European-Non Finnish (NFE) AF: 0.00984 AC: 133 AN: 13510

Other (OTH) AF: 0.00 AC: 0 AN: 458

Alfa AF: 0.0333 Hom.: 1333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.29
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs17222279; hg19: chrY-16839499;