11-78102951-CAAAAAA-CAA

Variant names:

• chr11-78102951-CAAAA-C
• rs35218171
• NM_024079.5:c.1349+1025_1349+1028delTTTT

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP6 BS1

The NM_001007027.3(ALG8):​c.1350-7_1350-4delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 119,646 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 Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000085 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0074 (0 hom.)
• Consequence: ALG8 NM_001007027.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 11-78102951-CAAAA-C is Benign according to our data. Variant chr11-78102951-CAAAA-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00743 (12/1614) while in subpopulation EAS AF= 0.0192 (1/52). AF 95% confidence interval is 0.00626. There are 0 homozygotes in gnomad4_exome. There are 10 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG8	NM_024079.5	c.1349+1025_1349+1028delTTTT		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+1025_1349+1028delTTTT		intron_variant	Intron 12 of 12	1	NM_024079.5	ENSP00000299626.5

Frequencies

GnomAD3 genomes AF: 0.00000847 AC: 1 AN: 118032 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000182

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00794 AC: 1 AN: 126 Hom.: 0 AF XY: 0.0132 AC XY: 1 AN XY: 76

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00743 AC: 12 AN: 1614 Hom.: 0 AF XY: 0.00931 AC XY: 10 AN XY: 1074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0192

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0115

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000847 AC: 1 AN: 118032 Hom.: 0 Cov.: 0 AF XY: 0.0000178 AC XY: 1 AN XY: 56152

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000182

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs35218171; hg19: chr11-77813997;