6-116462113-GCG-AGC

Variant names:

• chr6-116462113-GCG-AGC
• NM_001010919.3:c.184_186delGCGinsAGC
• CALHM6 p.Ala62Ser

Variant summary

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

The NM_001010919.3(CALHM6):​c.184_186delGCGinsAGC​(p.Ala62Ser) variant causes a missense change involving the alteration of a non-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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CALHM6 NM_001010919.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

Genes affected

CALHM6 (HGNC:33391): (calcium homeostasis modulator family member 6) Predicted to enable cation channel activity. Predicted to be involved in cation transmembrane transport. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285446 (HGNC:):

CALHM6-AS1 (HGNC:40971): (CALHM6 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010919.3. 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
	CALHM6	NM_001010919.3	MANE Select	c.184_186delGCGinsAGC	p.Ala62Ser	missense	N/A	NP_001010919.1	Q5R3K3-1
	CALHM6	NM_001276460.2		c.9+684_9+686delGCGinsAGC		intron	N/A	NP_001263389.1	Q5R3K3-2
	CALHM6-AS1	NR_174951.1		n.87-921_87-919delCGCinsGCT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM6	ENST00000368605.3	TSL:5 MANE Select	c.184_186delGCGinsAGC	p.Ala62Ser	missense	N/A	ENSP00000357594.1	Q5R3K3-1
	ENSG00000285446	ENST00000644499.1		c.767-1170_767-1168delGCGinsAGC		intron	N/A	ENSP00000495266.1	A0A2R8Y6J1
	CALHM6	ENST00000859968.1		c.184_186delGCGinsAGC	p.Ala62Ser	missense	N/A	ENSP00000530027.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

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: chr6-116783276;