rs1156562439

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001215.4(CA6):​c.98C>A​(p.Ala33Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. A33V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CA6
NM_001215.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.02690357).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CA6NM_001215.4 linkc.98C>A p.Ala33Glu missense_variant Exon 2 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.98C>A p.Ala33Glu missense_variant Exon 2 of 8 1 NM_001215.4 ENSP00000366662.2 P23280-1
CA6ENST00000480186.7 linkc.98C>A p.Ala33Glu missense_variant Exon 2 of 3 2 ENSP00000435280.1 Q8N4G4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1450620
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
721626
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:
0.00000181
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
Benign
0.11
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
0.0020
DANN
Benign
0.28
DEOGEN2
Benign
0.0041
.;T;T;.
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.26
T;T;T;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.027
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.30
.;.;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.57
N;N;N;N
REVEL
Benign
0.075
Sift
Benign
0.87
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0020
.;.;B;.
Vest4
0.12, 0.10, 0.10
MutPred
0.38
Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);
MVP
0.28
MPC
0.17
ClinPred
0.033
T
GERP RS
-11
Varity_R
0.16
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr1-9009340; API