11-78102951-CAAAAAA-CAAAAAAAA

Variant names:

• chr11-78102951-C-CAA
• rs35218171
• NM_024079.5:c.1349+1027_1349+1028dupTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_001007027.3(ALG8):​c.1350-5_1350-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000076 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0062 (0 hom.)
• Consequence: ALG8 NM_001007027.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

Genes affected

ALG8 (HGNC:23161): (ALG8 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins. Mutations in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ih). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00616 (10/1624) while in subpopulation EAS AF= 0.037 (2/54). AF 95% confidence interval is 0.00658. There are 0 homozygotes in gnomad4_exome. There are 8 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG8	NM_024079.5	c.1349+1027_1349+1028dupTT		intron_variant	Intron 12 of 12	ENST00000299626.10	NP_076984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG8	ENST00000299626.10	c.1349+1028_1349+1029insTT		intron_variant	Intron 12 of 12	1	NM_024079.5	ENSP00000299626.5

Frequencies

GnomAD3 genomes AF: 0.0000762 AC: 9 AN: 118046 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000936

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000241

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000157

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000182

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0159 AC: 2 AN: 126 Hom.: 0 AF XY: 0.0263 AC XY: 2 AN XY: 76

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0294

Gnomad ASJ exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad NFE exome AF: 0.0167

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00616 AC: 10 AN: 1624 Hom.: 0 Cov.: 0 AF XY: 0.00738 AC XY: 8 AN XY: 1084

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0370

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00688

Gnomad4 OTH exome AF: 0.00943

GnomAD4 genome AF: 0.0000762 AC: 9 AN: 118034 Hom.: 0 Cov.: 0 AF XY: 0.0000890 AC XY: 5 AN XY: 56182

Gnomad4 AFR AF: 0.0000935

Gnomad4 AMR AF: 0.000263

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000242

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000157

Gnomad4 NFE AF: 0.0000182

Gnomad4 OTH AF: 0.00

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: rs35218171; hg19: chr11-77813997;