NM_001129742.2:c.649A>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001129742.2(CALHM3):​c.649A>C​(p.Ser217Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. S217G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

CALHM3
NM_001129742.2 missense

Scores

3
9
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.51
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CALHM3NM_001129742.2 linkc.649A>C p.Ser217Arg 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.649A>C p.Ser217Arg missense_variant Exon 3 of 3 1 NM_001129742.2 ENSP00000358798.4 Q86XJ0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399046
Hom.:
0
Cov.:
34
AF XY:
0.00000145
AC XY:
1
AN XY:
690044
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Uncertain
0.025
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.035
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.79
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.27
Sift
Benign
0.063
T
Sift4G
Pathogenic
0.0
D
Vest4
0.75
MutPred
0.38
Gain of MoRF binding (P = 0.0202);
MVP
0.20
ClinPred
1.0
D
GERP RS
5.7
Varity_R
0.55
gMVP
0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-105233356; API