6-116462390-C-A

Variant names:

• chr6-116462390-C-A
• rs755445117
• NM_001010919.3:c.461C>A

Variant summary

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

The NM_001010919.3(CALHM6):​c.461C>A​(p.Pro154Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000515 in 1,320,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P154L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: CALHM6 NM_001010919.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.28
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.461C>A	p.Pro154Gln	missense	Exon 2 of 3	NP_001010919.1	Q5R3K3-1
	CALHM6	NM_001276460.2		c.10-893C>A		intron	N/A	NP_001263389.1	Q5R3K3-2
	CALHM6-AS1	NR_174951.1		n.87-1196G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM6	ENST00000368605.3	TSL:5 MANE Select	c.461C>A	p.Pro154Gln	missense	Exon 2 of 3	ENSP00000357594.1	Q5R3K3-1
	ENSG00000285446	ENST00000644499.1		c.767-893C>A		intron	N/A	ENSP00000495266.1	A0A2R8Y6J1
	CALHM6	ENST00000859968.1		c.461C>A	p.Pro154Gln	missense	Exon 1 of 2	ENSP00000530027.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000515 AC: 68 AN: 1320848 Hom.: 0 Cov.: 33 AF XY: 0.0000461 AC XY: 30 AN XY: 650248

African (AFR) AF: 0.0000384 AC: 1 AN: 26014

American (AMR) AF: 0.00 AC: 0 AN: 24218

Ashkenazi Jewish (ASJ) AF: 0.0000446 AC: 1 AN: 22430

East Asian (EAS) AF: 0.00 AC: 0 AN: 28704

South Asian (SAS) AF: 0.00 AC: 0 AN: 71826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4042

European-Non Finnish (NFE) AF: 0.0000621 AC: 65 AN: 1046640

Other (OTH) AF: 0.0000184 AC: 1 AN: 54312

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.72	T
PhyloP100		5.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.63		Loss of catalytic residue at P154 (P = 0.0042)
MVP		0.61
MPC		0.45
ClinPred		1.0	D
GERP RS		4.8
PromoterAI		-0.043	Neutral
Varity_R		0.64
gMVP		0.76
Mutation Taster		=50/50

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: rs755445117; hg19: chr6-116783553;