10-103473437-G-C

Variant names:

• chr10-103473437-G-C
• rs772062343
• NM_001129742.2:c.811C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001129742.2(CALHM3):​c.811C>G​(p.Pro271Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000412 in 1,530,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P271S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: CALHM3 NM_001129742.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.569
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.039286643).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129742.2. 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
	CALHM3	NM_001129742.2	MANE Select	c.811C>G	p.Pro271Ala	missense	Exon 3 of 3	NP_001123214.1	Q86XJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM3	ENST00000369783.4	TSL:1 MANE Select	c.811C>G	p.Pro271Ala	missense	Exon 3 of 3	ENSP00000358798.4	Q86XJ0

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152234 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000727 AC: 10 AN: 137642 AF XY: 0.0000691

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000433

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000297 AC: 41 AN: 1378474 Hom.: 0 Cov.: 34 AF XY: 0.0000295 AC XY: 20 AN XY: 677114

African (AFR) AF: 0.00 AC: 0 AN: 31310

American (AMR) AF: 0.000262 AC: 9 AN: 34316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23640

East Asian (EAS) AF: 0.00 AC: 0 AN: 35470

South Asian (SAS) AF: 0.00 AC: 0 AN: 75628

European-Finnish (FIN) AF: 0.0000417 AC: 2 AN: 47990

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5610

European-Non Finnish (NFE) AF: 0.0000272 AC: 29 AN: 1067382

Other (OTH) AF: 0.00 AC: 0 AN: 57128

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152234 Hom.: 0 Cov.: 34 AF XY: 0.000188 AC XY: 14 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.00131 AC: 20 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000390 Hom.: 0

Bravo AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.95
DANN	Benign	0.45
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.57
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.028
Sift	Benign	0.28	T
Sift4G	Benign	0.29	T
Vest4		0.062
MutPred		0.28		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.076
ClinPred		0.060	T
GERP RS		2.7
Varity_R		0.018
gMVP		0.18
Mutation Taster		=97/3	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: rs772062343; hg19: chr10-105233194;