chr16-87888165-C-T

Variant names:

• chr16-87888165-C-T
• rs150891997
• NM_001739.2:c.882G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001739.2(CA5A):​c.882G>A​(p.Ala294Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,613,814 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (3 hom.)
• Consequence: CA5A NM_001739.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.25

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]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-87888165-C-T is Benign according to our data. Variant chr16-87888165-C-T is described in ClinVar as [Benign]. Clinvar id is 791684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.25 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA5A	NM_001739.2	c.882G>A	p.Ala294Ala	synonymous_variant	Exon 7 of 7	ENST00000649794.3	NP_001730.1
CA5A	NM_001367225.1	c.774+3634G>A		intron_variant	Intron 6 of 6		NP_001354154.1
CA5A	NR_159798.1	n.1069G>A		non_coding_transcript_exon_variant	Exon 8 of 8
CA5A	NR_159799.1	n.842G>A		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA5A	ENST00000649794.3	c.882G>A	p.Ala294Ala	synonymous_variant	Exon 7 of 7		NM_001739.2	ENSP00000498065.2

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 296 AN: 152106 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000657 AC: 165 AN: 251100 AF XY: 0.000553

Gnomad AFR exome AF: 0.00769

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000289 AC: 422 AN: 1461590 Hom.: 3 Cov.: 31 AF XY: 0.000279 AC XY: 203 AN XY: 727102

Gnomad4 AFR exome AF: 0.00753 AC: 252 AN: 33472

Gnomad4 AMR exome AF: 0.000559 AC: 25 AN: 44714

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26128

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39698

Gnomad4 SAS exome AF: 0.000568 AC: 49 AN: 86238

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53420

Gnomad4 NFE exome AF: 0.0000396 AC: 44 AN: 1111788

Gnomad4 Remaining exome AF: 0.000861 AC: 52 AN: 60370

GnomAD4 genome AF: 0.00194 AC: 295 AN: 152224 Hom.: 2 Cov.: 32 AF XY: 0.00172 AC XY: 128 AN XY: 74434

Gnomad4 AFR AF: 0.00674 AC: 0.00674309 AN: 0.00674309

Gnomad4 AMR AF: 0.000523 AC: 0.000523218 AN: 0.000523218

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000415 AC: 0.00041511 AN: 0.00041511

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000588 AC: 0.0000588132 AN: 0.0000588132

Gnomad4 OTH AF: 0.000473 AC: 0.000473037 AN: 0.000473037

Alfa AF: 0.00123 Hom.: 1

Bravo AF: 0.00238

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency Benign:1

Dec 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.13
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs150891997; hg19: chr16-87921771; COSMIC: COSV59239567; COSMIC: COSV59239567;