rs1210257970

Variant names:

• chr1-1054454-G-A
• rs1210257970
• NM_198576.4:c.5883G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-1054454-G-A
• chr1-1054454-G-C
• chr1-1054454-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_198576.4(AGRN):​c.5883G>A​(p.Gln1961Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AGRN NM_198576.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.126
• Publications: 0 publications found

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: DEFINITIVE, STRONG Submitted by: ClinGen, 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-1054454-G-A is Benign according to our data. Variant chr1-1054454-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 541179.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198576.4. 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
	AGRN	NM_198576.4	MANE Select	c.5883G>A	p.Gln1961Gln	synonymous	Exon 35 of 36	NP_940978.2
	AGRN	NM_001305275.2		c.5952G>A	p.Gln1984Gln	synonymous	Exon 38 of 39	NP_001292204.1	O00468-1
	AGRN	NM_001364727.2		c.5580G>A	p.Gln1860Gln	synonymous	Exon 35 of 36	NP_001351656.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGRN	ENST00000379370.7	TSL:1 MANE Select	c.5883G>A	p.Gln1961Gln	synonymous	Exon 35 of 36	ENSP00000368678.2	O00468-6
	AGRN	ENST00000461111.1	TSL:1	n.1999G>A		non_coding_transcript_exon	Exon 2 of 3
	AGRN	ENST00000651234.1		c.5637G>A	p.Gln1879Gln	synonymous	Exon 37 of 38	ENSP00000499046.1	A0A494C1I6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital myasthenic syndrome 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.27		Position offset: 19

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

Other links and lift over

dbSNP: rs1210257970; hg19: chr1-989834;