NM_001365588.1:c.2136C>T

Variant names:

• chrY-14840887-C-T
• rs373089425
• NM_001365588.1:c.2136C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001365588.1(NLGN4Y):​c.2136C>T​(p.Ala712Ala) 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: 0)
  • Exomes 𝑓: 0.000022 (0 hom. 8 hem.)
  • Failed GnomAD Quality Control
• Consequence: NLGN4Y NM_001365588.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.43
• Publications: 1 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant Y-14840887-C-T is Benign according to our data. Variant chrY-14840887-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.43 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.2136C>T	p.Ala712Ala	synonymous	Exon 7 of 7	NP_001352517.1	B4DHI3
	NLGN4Y	NM_001365584.1		c.2136C>T	p.Ala712Ala	synonymous	Exon 7 of 7	NP_001352513.1	B4DHI3
	NLGN4Y	NM_001365586.1		c.2136C>T	p.Ala712Ala	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.2136C>T	p.Ala712Ala	synonymous	Exon 7 of 7	ENSP00000510011.1	B4DHI3
	NLGN4Y	ENST00000382868.5	TSL:1	c.2247C>T	p.Ala749Ala	synonymous	Exon 8 of 8	ENSP00000372320.1	A6NMU8
	NLGN4Y	ENST00000339174.9	TSL:1	c.2076C>T	p.Ala692Ala	synonymous	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: 0.0000221 AC: 8 AN: 362576 Hom.: 0 Cov.: 4 AF XY: 0.0000221 AC XY: 8 AN XY: 362576

African (AFR) AF: 0.00 AC: 0 AN: 7038

American (AMR) AF: 0.00 AC: 0 AN: 9508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6734

East Asian (EAS) AF: 0.00 AC: 0 AN: 9488

South Asian (SAS) AF: 0.00 AC: 0 AN: 32075

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12869

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1626

European-Non Finnish (NFE) AF: 0.0000297 AC: 8 AN: 268979

Other (OTH) AF: 0.00 AC: 0 AN: 14259

GnomAD4 genome Cov.: 0

Alfa AF: 0.0957 Hom.: 249

ClinVar

ClinVar submissions

Significance: Likely benign

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_noAF	Benign	-0.66
CADD	Benign	0.36
DANN	Benign	0.51
PhyloP100		-1.4
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: rs373089425; hg19: chrY-16952767; COSMIC: COSV59294032;