rs202165284

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_001365925.2(NLGN1):c.67C>T(p.Arg23Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R23Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

NLGN1
NM_001365925.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.274

Publications

5 publications found

Variant links:

Genes affected

NLGN1 (HGNC:14291): (neuroligin 1) This gene encodes a member of 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. [provided by RefSeq, Jul 2008]

NLGN1 Gene-Disease associations (from GenCC):

autism, susceptibility to, 20
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

NLGN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.297845).

BP6

Variant 3-173604665-C-T is Benign according to our data. Variant chr3-173604665-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3879810.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 7 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365925.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLGN1	NM_001365925.2	MANE Select	c.67C>T	p.Arg23Trp	missense	Exon 2 of 7	NP_001352854.1	A0A8Q3SHM6
NLGN1	NM_001365923.2		c.67C>T	p.Arg23Trp	missense	Exon 2 of 7	NP_001352852.1
NLGN1	NM_001365924.2		c.67C>T	p.Arg23Trp	missense	Exon 2 of 7	NP_001352853.1	A0A8Q3SHM6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLGN1	ENST00000695368.1	MANE Select	c.67C>T	p.Arg23Trp	missense	Exon 2 of 7	ENSP00000511841.1	A0A8Q3SHM6
NLGN1	ENST00000415045.2	TSL:1	c.67C>T	p.Arg23Trp	missense	Exon 2 of 8	ENSP00000410374.2	C9J4D3
NLGN1	ENST00000361589.8	TSL:1	c.67C>T	p.Arg23Trp	missense	Exon 2 of 6	ENSP00000354541.4	Q8N2Q7-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000679

AC:

AN:

250396

AF XY:

0.0000665

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000609

AC:

AN:

1461462

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727036

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33432

American (AMR)

AF:

0.000224

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.000371

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

1111724

Other (OTH)

AF:

0.0000828

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41530

American (AMR)

AF:

0.0000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000415

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.046

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.67

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.025

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.81

PhyloP100

0.27

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.46

REVEL

Benign

0.21

Sift

Uncertain

0.026

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.39

MutPred

0.76

Loss of methylation at R23 (P = 0.0143)

MVP

0.63

MPC

0.42

ClinPred

0.056

GERP RS

0.26

gMVP

0.44

Mutation Taster

=86/14

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over