rs772062343

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 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: not found (cov: 34)
Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

CALHM3
NM_001129742.2 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.569
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.057833076).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CALHM3NM_001129742.2 linkc.811C>T p.Pro271Ser missense_variant Exon 3 of 3 ENST00000369783.4 NP_001123214.1 Q86XJ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CALHM3ENST00000369783.4 linkc.811C>T p.Pro271Ser missense_variant Exon 3 of 3 1 NM_001129742.2 ENSP00000358798.4 Q86XJ0

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.0000291
AC:
4
AN:
137642
Hom.:
0
AF XY:
0.0000276
AC XY:
2
AN XY:
72344
show subpopulations
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 SAS exome
AF:
0.00
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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000113
Gnomad4 SAS exome
AF:
0.0000529
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000187
Gnomad4 OTH exome
AF:
0.0000175
GnomAD4 genome
Cov.:
34
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
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

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs772062343; hg19: chr10-105233194; API