rs149659540

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1

The NM_198576.4(AGRN):c.5466A>G(p.Ser1822Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,573,372 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

AGRN
NM_198576.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.04

Publications

0 publications found

Variant links:

Genes affected

AGRN (HGNC:329): (agrin) This gene encodes one of several proteins that are critical in the development of the neuromuscular junction (NMJ), as identified in mouse knock-out studies. The encoded protein contains several laminin G, Kazal type serine protease inhibitor, and epidermal growth factor domains. Additional post-translational modifications occur to add glycosaminoglycans and disulfide bonds. In one family with congenital myasthenic syndrome affecting limb-girdle muscles, a mutation in this gene was found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]

AGRN Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 8
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
presynaptic congenital myasthenic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AGRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.049).

BP6

Variant 1-1051548-A-G is Benign according to our data. Variant chr1-1051548-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 541183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.04 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00215 (327/152320) while in subpopulation AFR AF = 0.00741 (308/41584). AF 95% confidence interval is 0.00673. There are 0 homozygotes in GnomAd4. There are 175 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGRN	NM_198576.4 link	c.5466A>G	p.Ser1822Ser	synonymous_variant	Exon 32 of 36	ENST00000379370.7	NP_940978.2	O00468-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGRN	ENST00000379370.7 link	c.5466A>G	p.Ser1822Ser	synonymous_variant	Exon 32 of 36	1	NM_198576.4	ENSP00000368678.2	O00468-6
AGRN	ENST00000651234.1 link	c.5163A>G	p.Ser1721Ser	synonymous_variant	Exon 32 of 38			ENSP00000499046.1	A0A494C1I6
AGRN	ENST00000652369.2 link	c.5151A>G	p.Ser1717Ser	synonymous_variant	Exon 31 of 35			ENSP00000498543.1	A0A494C0G5
AGRN	ENST00000620552.4 link	c.5064A>G	p.Ser1688Ser	synonymous_variant	Exon 33 of 39	5		ENSP00000484607.1	A0A087X208

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

326

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00740

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000915

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000607

AC:

119

AN:

195964

AF XY:

0.000522

show subpopulations

Gnomad AFR exome

AF:

0.00747

Gnomad AMR exome

AF:

0.000735

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000633

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000710

Gnomad OTH exome

AF:

0.000403

GnomAD4 exome

AF:

0.000196

AC:

279

AN:

1421052

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

123

AN XY:

702440

show subpopulations

African (AFR)

AF:

0.00631

AC:

207

AN:

32808

American (AMR)

AF:

0.000832

AC:

AN:

40862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24722

East Asian (EAS)

AF:

0.0000260

AC:

AN:

38432

South Asian (SAS)

AF:

0.0000491

AC:

AN:

81514

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47728

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5572

European-Non Finnish (NFE)

AF:

0.00000917

AC:

AN:

1090746

Other (OTH)

AF:

0.000375

AC:

AN:

58668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.00215

AC:

327

AN:

152320

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00741

AC:

308

AN:

41584

American (AMR)

AF:

0.000914

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68006

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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:

0.000787

Hom.:

Bravo

AF:

0.00235

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 03, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital myasthenic syndrome 8

Benign:1

Dec 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.1

(source)

DANN

Benign

0.65

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over