11-78139471-C-T

Variant names:

• chr11-78139471-C-T
• rs10793289
• NM_024079.5:c.95+23G>A

Variant summary

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

The NM_024079.5(ALG8):​c.95+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ALG8 NM_024079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.789
• Publications: 0 publications found

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]

KCTD21-AS1 (HGNC:48674): (KCTD21 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024079.5. 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
	ALG8	NM_024079.5	MANE Select	c.95+23G>A		intron	N/A	NP_076984.2	A0A024R5K5
	ALG8	NM_001425224.1		c.95+23G>A		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.95+23G>A		intron	N/A	NP_001412154.1	H0YDD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000299626.10	TSL:1 MANE Select	c.95+23G>A		intron	N/A	ENSP00000299626.5	Q9BVK2-1
	ALG8	ENST00000532050.5	TSL:1	n.95+23G>A		intron	N/A	ENSP00000437199.1	E9PNE2
	ALG8	ENST00000681699.1		c.-920G>A		5_prime_UTR	Exon 1 of 14	ENSP00000504969.1	A0A7P0T810

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400080 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 690658

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31650

American (AMR) AF: 0.00 AC: 0 AN: 35776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25190

East Asian (EAS) AF: 0.00 AC: 0 AN: 35854

South Asian (SAS) AF: 0.00 AC: 0 AN: 79302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1079220

Other (OTH) AF: 0.00 AC: 0 AN: 58048

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Benign	0.96
PhyloP100		0.79
PromoterAI		-0.074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: 23

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

Other links and lift over

dbSNP: rs10793289; hg19: chr11-77850517;