rs10793289

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-78139471-C-A
• chr11-78139471-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024079.5(ALG8):​c.95+23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,552,016 control chromosomes in the GnomAD database, including 151,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12012 hom., cov: 34)
  • Exomes 𝑓: 0.44 (139933 hom.)
• Consequence: ALG8 NM_024079.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.789
• Publications: 25 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 11-78139471-C-A is Benign according to our data. Variant chr11-78139471-C-A is described in ClinVar as Benign. ClinVar VariationId is 261685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	NM_024079.5	MANE Select	c.95+23G>T		intron	N/A	NP_076984.2
	ALG8	NM_001425224.1		c.95+23G>T		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.95+23G>T		intron	N/A	NP_001412154.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000299626.10	TSL:1 MANE Select	c.95+23G>T		intron	N/A	ENSP00000299626.5
	ALG8	ENST00000532050.5	TSL:1	n.95+23G>T		intron	N/A	ENSP00000437199.1
	ALG8	ENST00000679685.1		n.-931G>T		non_coding_transcript_exon	Exon 1 of 11	ENSP00000505698.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57696 AN: 152078 Hom.: 11999 Cov.: 34

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.391

GnomAD2 exomes AF: 0.423 AC: 66564 AN: 157346 AF XY: 0.425

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.370

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.373

Gnomad FIN exome AF: 0.548

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.444 AC: 621005 AN: 1399820 Hom.: 139933 Cov.: 34 AF XY: 0.444 AC XY: 306637 AN XY: 690562

African (AFR) AF: 0.185 AC: 5850 AN: 31646

American (AMR) AF: 0.372 AC: 13320 AN: 35772

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 10522 AN: 25188

East Asian (EAS) AF: 0.323 AC: 11571 AN: 35852

South Asian (SAS) AF: 0.416 AC: 32990 AN: 79298

European-Finnish (FIN) AF: 0.538 AC: 26539 AN: 49342

Middle Eastern (MID) AF: 0.383 AC: 2180 AN: 5696

European-Non Finnish (NFE) AF: 0.457 AC: 493359 AN: 1078988

Other (OTH) AF: 0.425 AC: 24674 AN: 58038

GnomAD4 genome AF: 0.379 AC: 57725 AN: 152196 Hom.: 12012 Cov.: 34 AF XY: 0.383 AC XY: 28522 AN XY: 74416

African (AFR) AF: 0.199 AC: 8260 AN: 41560

American (AMR) AF: 0.368 AC: 5626 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1461 AN: 3468

East Asian (EAS) AF: 0.373 AC: 1930 AN: 5170

South Asian (SAS) AF: 0.425 AC: 2051 AN: 4822

European-Finnish (FIN) AF: 0.549 AC: 5817 AN: 10592

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31273 AN: 67978

Other (OTH) AF: 0.397 AC: 840 AN: 2114

Alfa AF: 0.418 Hom.: 19558

Bravo AF: 0.358

Asia WGS AF: 0.424 AC: 1479 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ALG8 congenital disorder of glycosylation (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Benign	0.93
PhyloP100		0.79
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		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; COSMIC: COSV55199772; COSMIC: COSV55199772;