NM_001216.3:c.329T>A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001216.3(CA9):c.329T>A(p.Leu110*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,006 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. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
CA9
NM_001216.3 stop_gained
NM_001216.3 stop_gained
Scores
1
1
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.835
Publications
0 publications found
Genes affected
CA9 (HGNC:1383): (carbonic anhydrase 9) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA IX is a transmembrane protein and is one of only two tumor-associated carbonic anhydrase isoenzymes known. It is expressed in all clear-cell renal cell carcinoma, but is not detected in normal kidney or most other normal tissues. It may be involved in cell proliferation and transformation. This gene was mapped to 17q21.2 by fluorescence in situ hybridization, however, radiation hybrid mapping localized it to 9p13-p12. [provided by RefSeq, Jun 2014]
ARHGEF39 (HGNC:25909): (Rho guanine nucleotide exchange factor 39) Predicted to enable guanyl-nucleotide exchange factor activity. Involved in positive regulation of cell migration. Located in 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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001216.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CA9 | NM_001216.3 | MANE Select | c.329T>A | p.Leu110* | stop_gained | Exon 1 of 11 | NP_001207.2 | Q16790 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CA9 | ENST00000378357.9 | TSL:1 MANE Select | c.329T>A | p.Leu110* | stop_gained | Exon 1 of 11 | ENSP00000367608.4 | Q16790 | |
| ARHGEF39 | ENST00000490638.5 | TSL:1 | n.-573A>T | non_coding_transcript_exon | Exon 1 of 12 | ENSP00000436756.1 | Q8N4T4-2 | ||
| ARHGEF39 | ENST00000490638.5 | TSL:1 | n.-573A>T | 5_prime_UTR | Exon 1 of 12 | ENSP00000436756.1 | Q8N4T4-2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152140
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461866Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727240 show subpopulations
GnomAD4 exome
AF:
AC:
6
AN:
1461866
Hom.:
Cov.:
33
AF XY:
AC XY:
4
AN XY:
727240
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1111994
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome 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
GnomAD4 genome 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74316 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152140
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74316
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41426
American (AMR)
AF:
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68020
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
PhyloP100
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.