rs77325391

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001739.2(CA5A):c.135T>A(p.Asn45Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,612,282 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 112 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 104 hom. )

Consequence

CA5A
NM_001739.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.93

Publications

5 publications found

Variant links:

Genes affected

CA5A (HGNC:1377): (carbonic anhydrase 5A) 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 VA is localized in the mitochondria and expressed primarily in the liver. It may play an important role in ureagenesis and gluconeogenesis. CA5A gene maps to chromosome 16q24.3 and an unprocessed pseudogene has been assigned to 16p12-p11.2. [provided by RefSeq, Jul 2008]

CA5A Gene-Disease associations (from GenCC):

hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

CA5A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021915138).

BP6

Variant 16-87936316-A-T is Benign according to our data. Variant chr16-87936316-A-T is described in ClinVar as Benign. ClinVar VariationId is 380517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001739.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CA5A	NM_001739.2	MANE Select	c.135T>A	p.Asn45Lys	missense	Exon 1 of 7	NP_001730.1	P35218
CA5A	NM_001367225.1		c.135T>A	p.Asn45Lys	missense	Exon 1 of 7	NP_001354154.1	A0A3B3IRX9
CA5A	NR_159798.1		n.214T>A		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CA5A	ENST00000649794.3	MANE Select	c.135T>A	p.Asn45Lys	missense	Exon 1 of 7	ENSP00000498065.2	P35218
CA5A	ENST00000906212.1		c.135T>A	p.Asn45Lys	missense	Exon 1 of 8	ENSP00000576271.1
CA5A	ENST00000906206.1		c.135T>A	p.Asn45Lys	missense	Exon 1 of 8	ENSP00000576265.1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3385

AN:

151916

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0767

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00899

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.00581

AC:

1461

AN:

251304

AF XY:

0.00419

show subpopulations

Gnomad AFR exome

AF:

0.0756

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00231

AC:

3375

AN:

1460244

Hom.:

104

Cov.:

AF XY:

0.00201

AC XY:

1460

AN XY:

726564

show subpopulations

African (AFR)

AF:

0.0757

AC:

2530

AN:

33424

American (AMR)

AF:

0.00452

AC:

202

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00647

AC:

169

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.000116

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000119

AC:

132

AN:

1110592

Other (OTH)

AF:

0.00519

AC:

313

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

157

314

471

628

785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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

AF:

0.0223

AC:

3392

AN:

152038

Hom.:

112

Cov.:

AF XY:

0.0213

AC XY:

1585

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.0767

AC:

3179

AN:

41460

American (AMR)

AF:

0.00891

AC:

136

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

67990

Other (OTH)

AF:

0.0175

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

161

322

482

643

804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00414

Hom.:

Bravo

AF:

0.0249

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0726

AC:

319

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00716

AC:

869

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.052

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.023

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

PhyloP100

-1.9

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

REVEL

Benign

0.26

Sift

Uncertain

0.026

Sift4G

Benign

0.45

Polyphen

0.29

Vest4

0.11

MutPred

0.63

Gain of methylation at N45 (P = 0.0121)

MVP

0.26

MPC

0.046

ClinPred

0.012

GERP RS

-3.4

PromoterAI

0.028

Neutral

(source)

Varity_R

0.10

gMVP

0.30

Mutation Taster

=99/1

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over