11-78139763-C-T

Variant names:

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

Variant summary

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

The ENST00000667996.2(KCTD21-AS1):​n.32C>T 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 0.168 in 668,402 control chromosomes in the GnomAD database, including 10,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2441 hom., cov: 34)
  • Exomes 𝑓: 0.17 (7930 hom.)
• Consequence: KCTD21-AS1 ENST00000667996.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-78139763-C-T is Benign according to our data. Variant chr11-78139763-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

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>A		upstream_gene	N/A	NP_076984.2	A0A024R5K5
	ALG8	NM_001425224.1		c.-175G>A		upstream_gene	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.-175G>A		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>T		non_coding_transcript_exon	Exon 1 of 3
	KCTD21-AS1	ENST00000701360.2		n.8C>T		non_coding_transcript_exon	Exon 1 of 3
	KCTD21-AS1	ENST00000720968.1		n.62C>T		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26127 AN: 152098 Hom.: 2437 Cov.: 34

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.167 AC: 86114 AN: 516186 Hom.: 7930 Cov.: 6 AF XY: 0.169 AC XY: 46108 AN XY: 273280

African (AFR) AF: 0.220 AC: 3101 AN: 14080

American (AMR) AF: 0.0968 AC: 2388 AN: 24666

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 2460 AN: 15922

East Asian (EAS) AF: 0.288 AC: 9107 AN: 31580

South Asian (SAS) AF: 0.213 AC: 11153 AN: 52416

European-Finnish (FIN) AF: 0.118 AC: 3825 AN: 32538

Middle Eastern (MID) AF: 0.235 AC: 516 AN: 2196

European-Non Finnish (NFE) AF: 0.155 AC: 48685 AN: 314406

Other (OTH) AF: 0.172 AC: 4879 AN: 28382

GnomAD4 genome AF: 0.172 AC: 26139 AN: 152216 Hom.: 2441 Cov.: 34 AF XY: 0.169 AC XY: 12596 AN XY: 74410

African (AFR) AF: 0.219 AC: 9084 AN: 41522

American (AMR) AF: 0.114 AC: 1742 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1449 AN: 5168

South Asian (SAS) AF: 0.207 AC: 997 AN: 4828

European-Finnish (FIN) AF: 0.0965 AC: 1024 AN: 10606

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10718 AN: 68008

Other (OTH) AF: 0.171 AC: 360 AN: 2108

Alfa AF: 0.120 Hom.: 261

Bravo AF: 0.176

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.68
DANN	Benign	0.75
PhyloP100		-1.0
PromoterAI		0.090	Neutral
Mutation Taster		=100/0	polymorphism

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;