Y-14840785-C-T

Variant names:

• chrY-14840785-C-T
• rs767683335
• NM_001365588.1:c.2034C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001365588.1(NLGN4Y):​c.2034C>T​(p.Pro678Pro) variant causes a synonymous 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 Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 4)
  • Exomes 𝑓: 0.000018 (0 hom. 6 hem.)
  • Failed GnomAD Quality Control
• Consequence: NLGN4Y NM_001365588.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.81
• Publications: 2 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant Y-14840785-C-T is Benign according to our data. Variant chrY-14840785-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 770316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.

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.2034C>T	p.Pro678Pro	synonymous	Exon 7 of 7	NP_001352517.1	B4DHI3
	NLGN4Y	NM_001365584.1		c.2034C>T	p.Pro678Pro	synonymous	Exon 7 of 7	NP_001352513.1	B4DHI3
	NLGN4Y	NM_001365586.1		c.2034C>T	p.Pro678Pro	synonymous	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.2034C>T	p.Pro678Pro	synonymous	Exon 7 of 7	ENSP00000510011.1	B4DHI3
	NLGN4Y	ENST00000382868.5	TSL:1	c.2145C>T	p.Pro715Pro	synonymous	Exon 8 of 8	ENSP00000372320.1	A6NMU8
	NLGN4Y	ENST00000339174.9	TSL:1	c.1974C>T	p.Pro658Pro	synonymous	Exon 6 of 6	ENSP00000342535.5	Q8NFZ3-1

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD2 exomes AF: 0.0000314 AC: 2 AN: 63721 AF XY: 0.0000314

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000334

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000177 AC: 6 AN: 338505 Hom.: 0 Cov.: 24 AF XY: 0.0000177 AC XY: 6 AN XY: 338505

African (AFR) AF: 0.00 AC: 0 AN: 5939

American (AMR) AF: 0.000109 AC: 1 AN: 9154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6329

East Asian (EAS) AF: 0.00 AC: 0 AN: 8687

South Asian (SAS) AF: 0.00 AC: 0 AN: 30010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11867

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1509

European-Non Finnish (NFE) AF: 0.0000199 AC: 5 AN: 251766

Other (OTH) AF: 0.00 AC: 0 AN: 13244

GnomAD4 genome Cov.: 4

Alfa AF: 0.188 Hom.: 446

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.3
DANN	Benign	0.42
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs767683335; hg19: chrY-16952665; COSMIC: COSV59296056;