rs7049300

Variant names:

• chrX-5903745-G-A
• rs7049300
• NM_181332.3:c.933C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-5903745-G-A
• chrX-5903745-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_181332.3(NLGN4X):​c.933C>T​(p.Thr311Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,209,508 control chromosomes in the GnomAD database, including 6,131 homozygotes. There are 46,435 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (751 hom., 4089 hem., cov: 22)
  • Exomes 𝑓: 0.12 (5380 hom. 42346 hem.)
• Consequence: NLGN4X NM_181332.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.375
• Publications: 15 publications found

Genes affected

NLGN4X (HGNC:14287): (neuroligin 4 X-linked) This gene encodes a member of the type-B carboxylesterase/lipase protein family. The encoded protein belongs to a family of neuronal cell surface proteins. Members of this family may act as splice site-specific ligands for beta-neurexins and may be involved in the formation and remodeling of central nervous system synapses. The encoded protein interacts with discs large homolog 4 (DLG4). Mutations in this gene have been associated with autism and Asperger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

NLGN4X Gene-Disease associations (from GenCC):

• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• autism, susceptibility to, X-linked 2

  Inheritance: XL Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant X-5903745-G-A is Benign according to our data. Variant chrX-5903745-G-A is described in ClinVar as Benign. ClinVar VariationId is 95987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.375 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181332.3. 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
	NLGN4X	NM_181332.3	MANE Select	c.933C>T	p.Thr311Thr	synonymous	Exon 5 of 6	NP_851849.1	Q8N0W4-1
	NLGN4X	NM_001282145.2		c.933C>T	p.Thr311Thr	synonymous	Exon 6 of 7	NP_001269074.1	Q8N0W4-1
	NLGN4X	NM_001282146.2		c.933C>T	p.Thr311Thr	synonymous	Exon 5 of 6	NP_001269075.1	Q8N0W4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN4X	ENST00000381095.8	TSL:1 MANE Select	c.933C>T	p.Thr311Thr	synonymous	Exon 5 of 6	ENSP00000370485.3	Q8N0W4-1
	NLGN4X	ENST00000538097.6	TSL:1	c.993C>T	p.Thr331Thr	synonymous	Exon 5 of 6	ENSP00000439203.3	Q8N0W4-2
	NLGN4X	ENST00000275857.10	TSL:1	c.933C>T	p.Thr311Thr	synonymous	Exon 5 of 6	ENSP00000275857.6	Q8N0W4-1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 14341 AN: 111235 Hom.: 751 Cov.: 22

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.0852

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.0983

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.125

GnomAD2 exomes AF: 0.108 AC: 19778 AN: 183403 AF XY: 0.110

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.0416

Gnomad ASJ exome AF: 0.0920

Gnomad EAS exome AF: 0.107

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.118 AC: 129368 AN: 1098219 Hom.: 5380 Cov.: 34 AF XY: 0.116 AC XY: 42346 AN XY: 363575

African (AFR) AF: 0.180 AC: 4751 AN: 26403

American (AMR) AF: 0.0464 AC: 1633 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 1753 AN: 19386

East Asian (EAS) AF: 0.122 AC: 3678 AN: 30205

South Asian (SAS) AF: 0.0883 AC: 4781 AN: 54147

European-Finnish (FIN) AF: 0.112 AC: 4532 AN: 40529

Middle Eastern (MID) AF: 0.129 AC: 532 AN: 4137

European-Non Finnish (NFE) AF: 0.121 AC: 102196 AN: 842112

Other (OTH) AF: 0.120 AC: 5512 AN: 46096

GnomAD4 genome AF: 0.129 AC: 14357 AN: 111289 Hom.: 751 Cov.: 22 AF XY: 0.122 AC XY: 4089 AN XY: 33527

African (AFR) AF: 0.177 AC: 5398 AN: 30569

American (AMR) AF: 0.0822 AC: 869 AN: 10566

Ashkenazi Jewish (ASJ) AF: 0.0852 AC: 225 AN: 2641

East Asian (EAS) AF: 0.117 AC: 406 AN: 3484

South Asian (SAS) AF: 0.0900 AC: 237 AN: 2633

European-Finnish (FIN) AF: 0.0983 AC: 590 AN: 6001

Middle Eastern (MID) AF: 0.120 AC: 26 AN: 216

European-Non Finnish (NFE) AF: 0.118 AC: 6264 AN: 52985

Other (OTH) AF: 0.124 AC: 189 AN: 1523

Alfa AF: 0.114 Hom.: 924

Bravo AF: 0.132

EpiCase AF: 0.125

EpiControl AF: 0.128

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		0.38
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7049300; hg19: chrX-5821786; COSMIC: COSV52008315; COSMIC: COSV52008315;