Genetic Variant CA6:p.Pro156Arg (chr1-8958968-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001215.4(CA6):c.467C>G(p.Pro156Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P156T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CA6
NM_001215.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

Publications

0 publications found

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]

CA6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33630472).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001215.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CA6	NM_001215.4	MANE Select	c.467C>G	p.Pro156Arg	missense	Exon 4 of 8	NP_001206.2	P23280-1
CA6	NM_001270500.2		c.467C>G	p.Pro156Arg	missense	Exon 4 of 8	NP_001257429.1	P23280-2
CA6	NM_001270501.2		c.287C>G	p.Pro96Arg	missense	Exon 3 of 7	NP_001257430.1	P23280-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CA6	ENST00000377443.7	TSL:1 MANE Select	c.467C>G	p.Pro156Arg	missense	Exon 4 of 8	ENSP00000366662.2	P23280-1
CA6	ENST00000377436.6	TSL:1	c.467C>G	p.Pro156Arg	missense	Exon 4 of 8	ENSP00000366654.3	P23280-2
CA6	ENST00000377442.3	TSL:1	c.287C>G	p.Pro96Arg	missense	Exon 3 of 7	ENSP00000366661.2	P23280-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460664

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111050

Other (OTH)

AF:

0.00

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.3

PhyloP100

2.1

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.17

Sift

Uncertain

0.0030

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.34

MutPred

0.55

Gain of solvent accessibility (P = 0.0411)

MVP

0.64

MPC

0.32

ClinPred

0.64

GERP RS

3.2

Varity_R

0.37

gMVP

0.64

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over