chr10-103473544-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001129742.2(CALHM3):​c.704C>T​(p.Ala235Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,551,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CALHM3
NM_001129742.2 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37

Publications

0 publications found
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CALHM3NM_001129742.2 linkc.704C>T p.Ala235Val 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>T p.Ala235Val missense_variant Exon 3 of 3 1 NM_001129742.2 ENSP00000358798.4 Q86XJ0

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000235
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000584
AC:
9
AN:
154230
AF XY:
0.0000608
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000153
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000137
AC:
192
AN:
1398842
Hom.:
0
Cov.:
34
AF XY:
0.000143
AC XY:
99
AN XY:
689948
show subpopulations
African (AFR)
AF:
0.0000633
AC:
2
AN:
31598
American (AMR)
AF:
0.00
AC:
0
AN:
35702
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25182
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35738
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79236
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48702
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5698
European-Non Finnish (NFE)
AF:
0.000174
AC:
188
AN:
1078978
Other (OTH)
AF:
0.0000345
AC:
2
AN:
58008
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.484
Heterozygous variant carriers
0
12
24
35
47
59
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74370
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41452
American (AMR)
AF:
0.00
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000235
AC:
16
AN:
68046
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.494
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000192
Hom.:
0
Bravo
AF:
0.0000680
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 02, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.704C>T (p.A235V) alteration is located in exon 3 (coding exon 3) of the CALHM3 gene. This alteration results from a C to T substitution at nucleotide position 704, causing the alanine (A) at amino acid position 235 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.66
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.19
T
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.060
D
MetaRNN
Uncertain
0.61
D
MetaSVM
Benign
-0.68
T
MutationAssessor
Uncertain
2.7
M
PhyloP100
7.4
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-3.5
D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0060
D
Vest4
0.60
MVP
0.24
ClinPred
0.88
D
GERP RS
5.7
Varity_R
0.53
gMVP
0.73
Mutation Taster
=59/41
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

Publications

Other links and lift over

dbSNP: rs761070737; hg19: chr10-105233301; COSMIC: COSV63922193; API