Y-14824201-C-T

Variant names:

• chrY-14824201-C-T
• rs35394227
• NM_001365588.1:c.699C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001365588.1(NLGN4Y):​c.699C>T​(p.Thr233Thr) 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (0 hom., 175 hem., cov: 0)
  • Exomes 𝑓: 0.0040 (0 hom. 1435 hem.)
  • Failed GnomAD Quality Control
• Consequence: NLGN4Y NM_001365588.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.652
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant Y-14824201-C-T is Benign according to our data. Variant chrY-14824201-C-T is described in ClinVar as Benign. ClinVar VariationId is 777318.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.652 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 175 YL gene

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.699C>T	p.Thr233Thr	synonymous	Exon 5 of 7	NP_001352517.1	B4DHI3
	NLGN4Y	NM_001365584.1		c.699C>T	p.Thr233Thr	synonymous	Exon 5 of 7	NP_001352513.1	B4DHI3
	NLGN4Y	NM_001365586.1		c.699C>T	p.Thr233Thr	synonymous	Exon 5 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.699C>T	p.Thr233Thr	synonymous	Exon 5 of 7	ENSP00000510011.1	B4DHI3
	NLGN4Y	ENST00000382868.5	TSL:1	c.810C>T	p.Thr270Thr	synonymous	Exon 6 of 8	ENSP00000372320.1	A6NMU8
	NLGN4Y	ENST00000339174.9	TSL:1	c.639C>T	p.Thr213Thr	synonymous	Exon 4 of 6	ENSP00000342535.5	Q8NFZ3-1

Frequencies

GnomAD3 genomes AF: 0.00529 AC: 175 AN: 33090 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000356

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000682

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0274

Gnomad NFE AF: 0.00415

Gnomad OTH AF: 0.00899

GnomAD2 exomes AF: 0.00588 AC: 396 AN: 67358 AF XY: 0.00588

Gnomad AFR exome AF: 0.000978

Gnomad AMR exome AF: 0.00970

Gnomad ASJ exome AF: 0.0542

Gnomad EAS exome AF: 0.000221

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00445

Gnomad OTH exome AF: 0.0113

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00395 AC: 1435 AN: 363052 Hom.: 0 Cov.: 0 AF XY: 0.00395 AC XY: 1435 AN XY: 363052

African (AFR) AF: 0.00212 AC: 15 AN: 7072

American (AMR) AF: 0.00958 AC: 91 AN: 9500

Ashkenazi Jewish (ASJ) AF: 0.0575 AC: 387 AN: 6734

East Asian (EAS) AF: 0.000211 AC: 2 AN: 9493

South Asian (SAS) AF: 0.00231 AC: 74 AN: 32060

European-Finnish (FIN) AF: 0.0000777 AC: 1 AN: 12871

Middle Eastern (MID) AF: 0.0357 AC: 56 AN: 1567

European-Non Finnish (NFE) AF: 0.00252 AC: 679 AN: 269480

Other (OTH) AF: 0.00911 AC: 130 AN: 14275

GnomAD4 genome AF: 0.00528 AC: 175 AN: 33155 Hom.: 0 Cov.: 0 AF XY: 0.00528 AC XY: 175 AN XY: 33155

African (AFR) AF: 0.000353 AC: 3 AN: 8487

American (AMR) AF: 0.0154 AC: 56 AN: 3629

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 53 AN: 763

East Asian (EAS) AF: 0.00 AC: 0 AN: 1253

South Asian (SAS) AF: 0.000680 AC: 1 AN: 1471

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3325

Middle Eastern (MID) AF: 0.0278 AC: 2 AN: 72

European-Non Finnish (NFE) AF: 0.00415 AC: 56 AN: 13497

Other (OTH) AF: 0.00893 AC: 4 AN: 448

Alfa AF: 0.0334 Hom.: 1121

ClinVar

ClinVar submissions

Significance: 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	-0.44
CADD	Benign	4.9
DANN	Benign	0.56
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs35394227; hg19: chrY-16936081;