X-15764659-T-A

Variant names:

• chrX-15764659-T-A
• NM_007220.4:c.224T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007220.4(CA5B):​c.224T>A​(p.Val75Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: CA5B NM_007220.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73
• Publications: 0 publications found

Genes affected

CA5B (HGNC:1378): (carbonic anhydrase 5B) 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. This gene encodes carbonic anhydrase 5B. CA5B, and the related CA5A gene, has its expression localized in the mitochondria though CA5B has a wider tissue distribution than CA5A, which is restricted to the liver, kidneys, and skeletal muscle. A carbonic anhydrase pseudogene (CA5BP1) is adjacent to the CA5B gene and these two loci produce CA5BP1-CA5B readthrough transcripts. [provided by RefSeq, Jan 2019]

CA5BP1-CA5B (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007220.4. 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
	CA5B	NM_007220.4	MANE Select	c.224T>A	p.Val75Asp	missense	Exon 3 of 8	NP_009151.1	Q9Y2D0
	CA5BP1-CA5B	NR_160544.1		n.988T>A		non_coding_transcript_exon	Exon 6 of 12
	CA5BP1-CA5B	NR_160545.1		n.988T>A		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5B	ENST00000318636.8	TSL:1 MANE Select	c.224T>A	p.Val75Asp	missense	Exon 3 of 8	ENSP00000314099.3	Q9Y2D0
	CA5B	ENST00000948118.1		c.224T>A	p.Val75Asp	missense	Exon 3 of 9	ENSP00000618177.1
	CA5B	ENST00000479740.5	TSL:3	c.224T>A	p.Val75Asp	missense	Exon 2 of 3	ENSP00000417553.1	C9JA11

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 21

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.98	D
Vest4		0.52
MutPred		0.50		Gain of disorder (P = 0.0059)
MVP		0.80
MPC		4.9
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.71
gMVP		0.87
Mutation Taster		=65/35	polymorphism

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

hg19: chrX-15782782;