16-87936316-A-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA5A	NM_001739.2 link	c.135T>A	p.Asn45Lys	missense_variant	Exon 1 of 7	ENST00000649794.3	NP_001730.1	P35218

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA5A	ENST00000649794.3 link	c.135T>A	p.Asn45Lys	missense_variant	Exon 1 of 7		NM_001739.2	ENSP00000498065.2		P35218

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

GnomAD3 exomes

AF:

0.00581

AC:

1461

AN:

251304

Hom.:

AF XY:

0.00419

AC XY:

569

AN XY:

135834

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 SAS 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

Gnomad4 AFR exome

AF:

0.0757

Gnomad4 AMR exome

AF:

0.00452

Gnomad4 ASJ exome

AF:

0.00647

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.00519

GnomAD4 genome

AF:

0.0223

AC:

3392

AN:

152038

Hom.:

112

Cov.:

AF XY:

0.0213

AC XY:

1585

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0767

Gnomad4 AMR

AF:

0.00891

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0175

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 04, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Feb 24, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency

Benign:1

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.052

DANN

Benign

0.71

DEOGEN2

Benign

0.023

T;.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.31

.;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

L;.;.;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

N;.;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.026

D;.;.;.

Sift4G

Benign

0.45

T;.;.;.

Polyphen

0.29

B;.;.;B

Vest4

0.11

MutPred

0.63

Gain of methylation at N45 (P = 0.0121);Gain of methylation at N45 (P = 0.0121);Gain of methylation at N45 (P = 0.0121);Gain of methylation at N45 (P = 0.0121);

MVP

0.26

MPC

0.046

ClinPred

0.012

GERP RS

-3.4

Varity_R

0.10

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over