X-15775292-C-G

Variant names:

• chrX-15775292-C-G
• rs757565475
• NM_007220.4:c.602C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_007220.4(CA5B):​c.602C>G​(p.Pro201Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,196,985 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P201L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000065 (0 hom. 3 hem.)
• Consequence: CA5B NM_007220.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• 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: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

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.602C>G	p.Pro201Arg	missense	Exon 6 of 8	NP_009151.1	Q9Y2D0
	CA5BP1-CA5B	NR_160544.1		n.2017C>G		non_coding_transcript_exon	Exon 10 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5B	ENST00000318636.8	TSL:1 MANE Select	c.602C>G	p.Pro201Arg	missense	Exon 6 of 8	ENSP00000314099.3	Q9Y2D0
	CA5B	ENST00000948118.1		c.602C>G	p.Pro201Arg	missense	Exon 6 of 9	ENSP00000618177.1
	CA5B	ENST00000496188.1	TSL:3	n.176C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112463 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000645 AC: 7 AN: 1084522 Hom.: 0 Cov.: 25 AF XY: 0.00000854 AC XY: 3 AN XY: 351240

African (AFR) AF: 0.00 AC: 0 AN: 26113

American (AMR) AF: 0.00 AC: 0 AN: 34289

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19085

East Asian (EAS) AF: 0.00 AC: 0 AN: 29968

South Asian (SAS) AF: 0.00 AC: 0 AN: 52065

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4036

European-Non Finnish (NFE) AF: 0.00000840 AC: 7 AN: 833264

Other (OTH) AF: 0.00 AC: 0 AN: 45508

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112463 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34629

African (AFR) AF: 0.0000323 AC: 1 AN: 30951

American (AMR) AF: 0.00 AC: 0 AN: 10662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3631

South Asian (SAS) AF: 0.00 AC: 0 AN: 2743

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6083

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53301

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.43
Sift	Benign	0.073	T
Sift4G	Benign	0.24	T
Polyphen		1.0	D
Vest4		0.78
MutPred		0.41		Gain of MoRF binding (P = 0.0137)
MVP		0.93
MPC		0.58
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.73
gMVP		0.71
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs757565475; hg19: chrX-15793415;