11-78139763-C-G

Variant names:

• chr11-78139763-C-G
• rs582266
• ENST00000667996.2:n.32C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000667996.2(KCTD21-AS1):​n.32C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000387 in 516,290 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: 0.0000039 (0 hom.)
• Consequence: KCTD21-AS1 ENST00000667996.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 4 publications found

Genes affected

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

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]

ALG8 Gene-Disease associations (from GenCC):

• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• ALG8-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• polycystic liver disease 3 with or without kidney cysts

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000667996.2. 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.-175G>C		upstream_gene	N/A	NP_076984.2	A0A024R5K5
	ALG8	NM_001425224.1		c.-175G>C		upstream_gene	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.-175G>C		upstream_gene	N/A	NP_001412154.1	H0YDD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD21-AS1	ENST00000667996.2		n.32C>G		non_coding_transcript_exon	Exon 1 of 3
	KCTD21-AS1	ENST00000701360.2		n.8C>G		non_coding_transcript_exon	Exon 1 of 3
	KCTD21-AS1	ENST00000720968.1		n.62C>G		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000387 AC: 2 AN: 516290 Hom.: 0 Cov.: 6 AF XY: 0.00000366 AC XY: 1 AN XY: 273340

African (AFR) AF: 0.00 AC: 0 AN: 14084

American (AMR) AF: 0.00 AC: 0 AN: 24676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15922

East Asian (EAS) AF: 0.00 AC: 0 AN: 31582

South Asian (SAS) AF: 0.00 AC: 0 AN: 52424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32538

Middle Eastern (MID) AF: 0.000455 AC: 1 AN: 2198

European-Non Finnish (NFE) AF: 0.00000318 AC: 1 AN: 314478

Other (OTH) AF: 0.00 AC: 0 AN: 28388

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.52
DANN	Benign	0.40
PhyloP100		-1.0
PromoterAI		0.0034	Neutral

Splicing

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

Other links and lift over

dbSNP: rs582266; hg19: chr11-77850809;