10-103473280-C-T

Variant names:

• chr10-103473280-C-T
• rs933732778
• NM_001129742.2:c.968G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001129742.2(CALHM3):​c.968G>A​(p.Gly323Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000478 in 1,463,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: CALHM3 NM_001129742.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05997002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM3	NM_001129742.2	c.968G>A	p.Gly323Asp	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.968G>A	p.Gly323Asp	missense_variant	Exon 3 of 3	1	NM_001129742.2	ENSP00000358798.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000458 AC: 6 AN: 1311322 Hom.: 0 Cov.: 29 AF XY: 0.00000785 AC XY: 5 AN XY: 637136

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: 0.00000579

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74364

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.97
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.064
Sift	Benign	0.63	T
Sift4G	Benign	0.67	T
Vest4		0.16
MutPred		0.20		Loss of catalytic residue at G323 (P = 0.0355);
MVP		0.085
ClinPred		0.13	T
GERP RS		4.6
Varity_R		0.060
gMVP		0.22

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: rs933732778; hg19: chr10-105233037;