rs755445117

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-116462390-C-A
• chr6-116462390-C-G
• chr6-116462390-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM6	NM_001010919.3	c.461C>A	p.Pro154Gln	missense_variant	Exon 2 of 3	ENST00000368605.3	NP_001010919.1
CALHM6	XM_011535845.4	c.461C>A	p.Pro154Gln	missense_variant	Exon 1 of 2		XP_011534147.1
CALHM6	NM_001276460.2	c.10-893C>A		intron_variant	Intron 1 of 1		NP_001263389.1
CALHM6-AS1	NR_174951.1	n.87-1196G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM6	ENST00000368605.3	c.461C>A	p.Pro154Gln	missense_variant	Exon 2 of 3	5	NM_001010919.3	ENSP00000357594.1
ENSG00000285446	ENST00000644499.1	c.767-893C>A		intron_variant	Intron 3 of 3			ENSP00000495266.1

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

Gnomad4 AFR exome AF: 0.0000384

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000446

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000621

Gnomad4 OTH exome AF: 0.0000184

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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
Varity_R		0.64
gMVP		0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs755445117; hg19: chr6-116783553;