Y-14840423-C-T

Variant names:

• chrY-14840423-C-T
• NM_001365588.1:c.1672C>T

Variant summary

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

The NM_001365588.1(NLGN4Y):​c.1672C>T​(p.Gln558*) variant causes a stop gained change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000083 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: NLGN4Y NM_001365588.1 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73
• 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 0 ACMG points.

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.1672C>T	p.Gln558*	stop_gained	Exon 7 of 7	NP_001352517.1	B4DHI3
	NLGN4Y	NM_001365584.1		c.1672C>T	p.Gln558*	stop_gained	Exon 7 of 7	NP_001352513.1	B4DHI3
	NLGN4Y	NM_001365586.1		c.1672C>T	p.Gln558*	stop_gained	Exon 7 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.1672C>T	p.Gln558*	stop_gained	Exon 7 of 7	ENSP00000510011.1	B4DHI3
	NLGN4Y	ENST00000382868.5	TSL:1	c.1783C>T	p.Gln595*	stop_gained	Exon 8 of 8	ENSP00000372320.1	A6NMU8
	NLGN4Y	ENST00000339174.9	TSL:1	c.1612C>T	p.Gln538*	stop_gained	Exon 6 of 6	ENSP00000342535.5	Q8NFZ3-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000826 AC: 3 AN: 363172 Hom.: 0 Cov.: 9 AF XY: 0.00000826 AC XY: 3 AN XY: 363172

African (AFR) AF: 0.00 AC: 0 AN: 7070

American (AMR) AF: 0.00 AC: 0 AN: 9510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6739

East Asian (EAS) AF: 0.00 AC: 0 AN: 9489

South Asian (SAS) AF: 0.00 AC: 0 AN: 32095

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1630

European-Non Finnish (NFE) AF: 0.0000111 AC: 3 AN: 269475

Other (OTH) AF: 0.00 AC: 0 AN: 14282

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
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	33
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.72	D
PhyloP100		3.7
Vest4		0.31
GERP RS		1.9
Mutation Taster		=61/139	disease causing

Splicing

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

Other links and lift over

hg19: chrY-16952303;