rs986549915

Variant names:

• chr10-103473464-C-A
• rs986549915
• NM_001129742.2:c.784G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-103473464-C-A
• chr10-103473464-C-G
• chr10-103473464-C-T

Variant summary

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

The NM_001129742.2(CALHM3):​c.784G>T​(p.Gly262Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,390,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. G262S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: CALHM3 NM_001129742.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.727
• Publications: 0 publications found

Genes affected

CALHM3 (HGNC:23458): (calcium homeostasis modulator 3) Predicted to enable cation channel activity. Predicted to be involved in ATP transport. Predicted to be located in basolateral plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.06803578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM3	NM_001129742.2	c.784G>T	p.Gly262Cys	missense_variant	Exon 3 of 3	ENST00000369783.4	NP_001123214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM3	ENST00000369783.4	c.784G>T	p.Gly262Cys	missense_variant	Exon 3 of 3	1	NM_001129742.2	ENSP00000358798.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000431 AC: 6 AN: 1390586 Hom.: 0 Cov.: 34 AF XY: 0.00000292 AC XY: 2 AN XY: 685258

African (AFR) AF: 0.00 AC: 0 AN: 30520

American (AMR) AF: 0.00 AC: 0 AN: 35002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24646

East Asian (EAS) AF: 0.00 AC: 0 AN: 35434

South Asian (SAS) AF: 0.00 AC: 0 AN: 78052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 0.00000558 AC: 6 AN: 1075314

Other (OTH) AF: 0.00 AC: 0 AN: 57588

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.3
DANN	Benign	0.62
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.73
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.69	N
REVEL	Benign	0.032
Sift	Benign	0.097	T
Sift4G	Benign	0.083	T
Vest4		0.10
MutPred		0.27		Loss of relative solvent accessibility (P = 0.0676);
MVP		0.31
ClinPred		0.10	T
GERP RS		2.6
Varity_R		0.077
gMVP		0.24
Mutation Taster		=92/8	polymorphism

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: rs986549915; hg19: chr10-105233221;