rs1556057385

Positions:

• chrY-14622379-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001365588.1(NLGN4Y):​c.260G>A​(p.Arg87Gln) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 0.0000028 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: NLGN4Y NM_001365588.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLGN4Y	NM_001365588.1	c.260G>A	p.Arg87Gln	missense_variant	2/7	ENST00000684976.1	NP_001352517.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLGN4Y	ENST00000684976.1	c.260G>A	p.Arg87Gln	missense_variant	2/7		NM_001365588.1	ENSP00000510011	A1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000275 AC: 1 AN: 363479 Hom.: 0 Cov.: 3 AF XY: 0.00000275 AC XY: 1 AN XY: 363479

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000371

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.74	.;D;.;D
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	1.0	D;.;D;D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MutationAssessor	Pathogenic	4.3	.;H;.;H
PROVEAN	Uncertain	-3.5	.;D;D;D
Sift	Pathogenic	0.0	.;D;D;D
Sift4G	Uncertain	0.0020	.;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.85, 0.81, 0.85
MVP		0.82
MPC		1.5
ClinPred		0.99	D
GERP RS		1.6
Varity_R		0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556057385; hg19: chrY-16734259; COSMIC: COSV52969676; COSMIC: COSV52969676;