NM_198576.4:c.4879+37_4879+41delGGGGG

Variant names:

• chr1-1050063-AGGGGG-A
• rs71576592
• NM_198576.4:c.4879+37_4879+41delGGGGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198576.4(AGRN):​c.4879+37_4879+41delGGGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 894,164 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: AGRN NM_198576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGRN	NM_198576.4	c.4879+37_4879+41delGGGGG		intron_variant	Intron 27 of 35	ENST00000379370.7	NP_940978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGRN	ENST00000379370.7	c.4879+27_4879+31delGGGGG		intron_variant	Intron 27 of 35	1	NM_198576.4	ENSP00000368678.2
AGRN	ENST00000651234.1	c.4564+27_4564+31delGGGGG		intron_variant	Intron 26 of 37			ENSP00000499046.1
AGRN	ENST00000652369.1	c.4564+27_4564+31delGGGGG		intron_variant	Intron 26 of 34			ENSP00000498543.1
AGRN	ENST00000620552.4	c.4465+27_4465+31delGGGGG		intron_variant	Intron 27 of 38	5		ENSP00000484607.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000224 AC: 2 AN: 894164 Hom.: 0 AF XY: 0.00000442 AC XY: 2 AN XY: 452324

Gnomad4 AFR exome AF: 0.0000881

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71576592; hg19: chr1-985443;