NM_004393.6:c.-116-4delT

Variant names:

• chr3-49510406-CT-C
• rs200455639
• NM_004393.6:c.-116-4delT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_004393.6(DAG1):​c.-116-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 773,566 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: DAG1 NM_004393.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.648

Genes affected

DAG1 (HGNC:2666): (dystroglycan 1) This gene encodes dystroglycan, a central component of dystrophin-glycoprotein complex that links the extracellular matrix and the cytoskeleton in the skeletal muscle. The encoded preproprotein undergoes O- and N-glycosylation, and proteolytic processing to generate alpha and beta subunits. Certain mutations in this gene are known to cause distinct forms of muscular dystrophy. Alternative splicing results in multiple transcript variants, all encoding the same protein. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-49510406-CT-C is Benign according to our data. Variant chr3-49510406-CT-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAG1	NM_004393.6	c.-116-4delT		splice_region_variant, intron_variant	Intron 1 of 2	ENST00000308775.7	NP_004384.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAG1	ENST00000308775.7	c.-116-4delT		splice_region_variant, intron_variant	Intron 1 of 2	1	NM_004393.6	ENSP00000312435.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.000171 AC: 132 AN: 773566 Hom.: 0 Cov.: 11 AF XY: 0.000178 AC XY: 73 AN XY: 409272

Gnomad4 AFR exome AF: 0.0000498

Gnomad4 AMR exome AF: 0.000100

Gnomad4 ASJ exome AF: 0.0000480

Gnomad4 EAS exome AF: 0.0000551

Gnomad4 SAS exome AF: 0.000512

Gnomad4 FIN exome AF: 0.0000263

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.000185

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs200455639; hg19: chr3-49547839;