NM_001129742.2:c.811C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001129742.2(CALHM3):​c.811C>T​(p.Pro271Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000798 in 1,378,474 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. 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. P271A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: CALHM3 NM_001129742.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057833076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM3	NM_001129742.2	c.811C>T	p.Pro271Ser	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.811C>T	p.Pro271Ser	missense_variant	Exon 3 of 3	1	NM_001129742.2	ENSP00000358798.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000291 AC: 4 AN: 137642 AF XY: 0.0000276

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000283

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000798 AC: 11 AN: 1378474 Hom.: 0 Cov.: 34 AF XY: 0.0000118 AC XY: 8 AN XY: 677114

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

American (AMR) AF: 0.00 AC: 0 AN: 34316

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

East Asian (EAS) AF: 0.000113 AC: 4 AN: 35470

South Asian (SAS) AF: 0.0000529 AC: 4 AN: 75628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1067382

Other (OTH) AF: 0.0000175 AC: 1 AN: 57128

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.5
DANN	Benign	0.57
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.57
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.013
Sift	Benign	0.24	T
Sift4G	Benign	0.33	T
Vest4		0.016
MutPred		0.23		Gain of phosphorylation at P271 (P = 0.0292);
MVP		0.076
ClinPred		0.026	T
GERP RS		2.7
Varity_R		0.023
gMVP		0.26
Mutation Taster		=96/4	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;