rs139579411

Variant names:

• chr10-103449409-C-A
• NM_015916.5:c.533G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-103449409-C-A
• chr10-103449409-C-G
• chr10-103449409-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015916.5(CALHM2):​c.533G>T​(p.Arg178Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,554 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: 6.8e-7 (0 hom.)
• Consequence: CALHM2 NM_015916.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.87

Genes affected

CALHM2 (HGNC:23493): (calcium homeostasis modulator family member 2) Predicted to enable cation channel activity. Involved in positive regulation of apoptotic process. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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
CALHM2	NM_015916.5	c.533G>T	p.Arg178Leu	missense_variant	Exon 3 of 4	ENST00000260743.10	NP_057000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM2	ENST00000260743.10	c.533G>T	p.Arg178Leu	missense_variant	Exon 3 of 4	1	NM_015916.5	ENSP00000260743.5
CALHM2	ENST00000369788.7	c.533G>T	p.Arg178Leu	missense_variant	Exon 3 of 4	2		ENSP00000358803.3
CALHM2	ENST00000494180.1	n.*216G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460554 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726608

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.73	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.99	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.059	B;B
Vest4		0.91
MutPred		0.52		Loss of disorder (P = 0.0245);Loss of disorder (P = 0.0245);
MVP		0.32
MPC		0.90
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.66
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-105209166;