dbSNP rs754657912: CA6:p.His19Pro (chr1-8945942-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001215.4(CA6):c.56A>C(p.His19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. H19L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CA6
NM_001215.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.141

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13021463).

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.56A>C	p.His19Pro	missense	Exon 1 of 8	NP_001206.2	P23280-1
CA6	NM_001270500.2		c.56A>C	p.His19Pro	missense	Exon 1 of 8	NP_001257429.1	P23280-2
CA6	NM_001270501.2		c.56A>C	p.His19Pro	missense	Exon 1 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.56A>C	p.His19Pro	missense	Exon 1 of 8	ENSP00000366662.2	P23280-1
CA6	ENST00000377436.6	TSL:1	c.56A>C	p.His19Pro	missense	Exon 1 of 8	ENSP00000366654.3	P23280-2
CA6	ENST00000377442.3	TSL:1	c.56A>C	p.His19Pro	missense	Exon 1 of 7	ENSP00000366661.2	P23280-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111686

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.029

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.50

M_CAP

Benign

0.064

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.88

PhyloP100

0.14

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.21

Sift

Uncertain

0.029

Sift4G

Benign

0.36

Polyphen

0.85

Vest4

0.42

MutPred

0.40

Gain of relative solvent accessibility (P = 0.1571)

MVP

0.71

MPC

0.69

ClinPred

0.75

GERP RS

2.1

PromoterAI

0.023

Neutral

(source)

Varity_R

0.31

gMVP

0.54

Mutation Taster

=90/10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over