10-103473544-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001129742.2(CALHM3):​c.704C>A​(p.Ala235Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,398,842 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.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

CALHM3
NM_001129742.2 missense

Scores

7
8
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.37
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CALHM3NM_001129742.2 linkc.704C>A p.Ala235Glu 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.704C>A p.Ala235Glu missense_variant Exon 3 of 3 1 NM_001129742.2 ENSP00000358798.4 Q86XJ0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000648
AC:
1
AN:
154230
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
82304
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000170
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000429
AC:
6
AN:
1398842
Hom.:
0
Cov.:
34
AF XY:
0.00000580
AC XY:
4
AN XY:
689948
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:
0.00000463
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.88
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.068
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Benign
-0.67
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-3.6
D
REVEL
Uncertain
0.54
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0030
D
Vest4
0.69
MutPred
0.77
Gain of disorder (P = 0.0857);
MVP
0.35
ClinPred
0.97
D
GERP RS
5.7
Varity_R
0.79
gMVP
0.89

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: rs761070737; hg19: chr10-105233301; API