1-8958967-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001215.4(CA6):​c.466C>A​(p.Pro156Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P156L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CA6
NM_001215.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.844
Variant links:
Genes affected
CA6 (HGNC:1380): (carbonic anhydrase 6) The protein encoded by this gene is one of several isozymes of carbonic anhydrase. This protein is found only in salivary glands and saliva and protein may play a role in the reversible hydratation of carbon dioxide though its function in saliva is unknown. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28703606).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CA6NM_001215.4 linkc.466C>A p.Pro156Thr missense_variant Exon 4 of 8 ENST00000377443.7 NP_001206.2 P23280-1B4DUH8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CA6ENST00000377443.7 linkc.466C>A p.Pro156Thr missense_variant Exon 4 of 8 1 NM_001215.4 ENSP00000366662.2 P23280-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 03, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.466C>A (p.P156T) alteration is located in exon 4 (coding exon 4) of the CA6 gene. This alteration results from a C to A substitution at nucleotide position 466, causing the proline (P) at amino acid position 156 to be replaced by a threonine (T). 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
Benign
0.19
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
.;T;.;.
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.067
N
LIST_S2
Uncertain
0.88
D;T;T;D
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.29
T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.7
.;M;M;.
PrimateAI
Benign
0.35
T
PROVEAN
Pathogenic
-5.9
D;D;D;D
REVEL
Benign
0.12
Sift
Uncertain
0.0050
D;D;D;D
Sift4G
Uncertain
0.019
D;D;D;D
Polyphen
0.92
.;P;.;.
Vest4
0.26, 0.26
MutPred
0.51
.;Loss of stability (P = 0.0713);Loss of stability (P = 0.0713);.;
MVP
0.58
MPC
0.44
ClinPred
0.84
D
GERP RS
1.0
Varity_R
0.37
gMVP
0.63

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: chr1-9019026; API