11-62631031-TG-GA

Variant names:

• chr11-62631031-TG-GA
• NM_198334.3:c.1148_1149delCAinsTC
• GANAB p.Thr383Ile

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5 PP3

The NM_198334.3(GANAB):​c.1148_1149delCAinsTC​(p.Thr383Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T383R) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GANAB NM_198334.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.91
• Publications: 0 publications found

Genes affected

GANAB (HGNC:4138): (glucosidase II alpha subunit) This gene encodes the alpha subunit of glucosidase II and a member of the glycosyl hydrolase 31 family of proteins. The heterodimeric enzyme glucosidase II plays a role in protein folding and quality control by cleaving glucose residues from immature glycoproteins in the endoplasmic reticulum. Expression of the encoded protein is elevated in lung tumor tissue and in response to UV irradiation. Mutations in this gene cause autosomal-dominant polycystic kidney and liver disease. [provided by RefSeq, Jul 2016]

GANAB Gene-Disease associations (from GenCC):

• polycystic kidney disease 3 with or without polycystic liver disease

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr11-62631032-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 253130.Status of the report is no_assertion_criteria_provided, 0 stars.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198334.3. 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
	GANAB	NM_198334.3	MANE Select	c.1148_1149delCAinsTC	p.Thr383Ile	missense splice_region	N/A	NP_938148.1	Q14697-1
	GANAB	NM_198335.4		c.1214_1215delCAinsTC	p.Thr405Ile	missense splice_region	N/A	NP_938149.2	Q14697-2
	GANAB	NM_001278192.2		c.872_873delCAinsTC	p.Thr291Ile	missense splice_region	N/A	NP_001265121.1	E9PKU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GANAB	ENST00000356638.8	TSL:1 MANE Select	c.1148_1149delCAinsTC	p.Thr383Ile	missense splice_region	N/A	ENSP00000349053.3	Q14697-1
	GANAB	ENST00000346178.8	TSL:1	c.1214_1215delCAinsTC	p.Thr405Ile	missense splice_region	N/A	ENSP00000340466.4	Q14697-2
	GANAB	ENST00000540933.5	TSL:1	c.857_858delCAinsTC	p.Thr286Ile	missense splice_region	N/A	ENSP00000442962.1	F5H6X6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-62398503;