NM_001010919.3:c.4G>C

Variant names:

• chr6-116461933-G-C
• rs1407304430
• NM_001010919.3:c.4G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010919.3(CALHM6):​c.4G>C​(p.Glu2Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. E2K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CALHM6 NM_001010919.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.93
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20513004).

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.4G>C	p.Glu2Gln	missense	Exon 2 of 3	NP_001010919.1	Q5R3K3-1
	CALHM6	NM_001276460.2		c.9+504G>C		intron	N/A	NP_001263389.1	Q5R3K3-2
	CALHM6-AS1	NR_174951.1		n.87-739C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM6	ENST00000368605.3	TSL:5 MANE Select	c.4G>C	p.Glu2Gln	missense	Exon 2 of 3	ENSP00000357594.1	Q5R3K3-1
	ENSG00000285446	ENST00000644499.1		c.767-1350G>C		intron	N/A	ENSP00000495266.1	A0A2R8Y6J1
	CALHM6	ENST00000859968.1		c.4G>C	p.Glu2Gln	missense	Exon 1 of 2	ENSP00000530027.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000793 AC: 1 AN: 126136 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000216

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0073	T
Eigen	Benign	0.076
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.9
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Benign	0.032	D
Sift4G	Uncertain	0.042	D
Polyphen		0.21	B
Vest4		0.085
MutPred		0.49		Gain of MoRF binding (P = 0.0068)
MVP		0.62
MPC		0.10
ClinPred		0.22	T
GERP RS		4.8
Varity_R		0.12
gMVP		0.53
Mutation Taster		=2/98	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1407304430; hg19: chr6-116783096;