rs2143888655

Variant names:

• chr16-87888228-C-T
• rs2143888655
• NM_001739.2:c.819G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001739.2(CA5A):​c.819G>A​(p.Glu273Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CA5A NM_001739.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.385
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 16-87888228-C-T is Benign according to our data. Variant chr16-87888228-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1117820.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.385 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5A	NM_001739.2	MANE Select	c.819G>A	p.Glu273Glu	synonymous	Exon 7 of 7	NP_001730.1	P35218
	CA5A	NM_001367225.1		c.774+3571G>A		intron	N/A	NP_001354154.1	A0A3B3IRX9
	CA5A	NR_159798.1		n.1006G>A		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5A	ENST00000649794.3	MANE Select	c.819G>A	p.Glu273Glu	synonymous	Exon 7 of 7	ENSP00000498065.2	P35218
	CA5A	ENST00000906212.1		c.954G>A	p.Glu318Glu	synonymous	Exon 8 of 8	ENSP00000576271.1
	CA5A	ENST00000906206.1		c.915G>A	p.Glu305Glu	synonymous	Exon 8 of 8	ENSP00000576265.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.68
DANN	Benign	0.83
PhyloP100		-0.39

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

Other links and lift over

dbSNP: rs2143888655; hg19: chr16-87921834;