NM_007220.4:c.355C>T

Variant names:

• chrX-15772510-C-T
• rs1931839771
• NM_007220.4:c.355C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_007220.4(CA5B):​c.355C>T​(p.Pro119Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,196,601 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: CA5B NM_007220.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899

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.355C>T	p.Pro119Ser	missense	Exon 4 of 8	NP_009151.1	Q9Y2D0
	CA5BP1-CA5B	NR_160544.1		n.1770C>T		non_coding_transcript_exon	Exon 8 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5B	ENST00000318636.8	TSL:1 MANE Select	c.355C>T	p.Pro119Ser	missense	Exon 4 of 8	ENSP00000314099.3	Q9Y2D0
	CA5B	ENST00000948118.1		c.355C>T	p.Pro119Ser	missense	Exon 4 of 9	ENSP00000618177.1
	CA5B	ENST00000479740.5	TSL:3	c.355C>T	p.Pro119Ser	missense	Exon 3 of 3	ENSP00000417553.1	C9JA11

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111888 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.00000184 AC: 2 AN: 1084713 Hom.: 0 Cov.: 26 AF XY: 0.00000285 AC XY: 1 AN XY: 351479

African (AFR) AF: 0.00 AC: 0 AN: 26107

American (AMR) AF: 0.00 AC: 0 AN: 35042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19256

East Asian (EAS) AF: 0.00 AC: 0 AN: 30084

South Asian (SAS) AF: 0.00 AC: 0 AN: 53595

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40491

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4091

European-Non Finnish (NFE) AF: 0.00000241 AC: 2 AN: 830428

Other (OTH) AF: 0.00 AC: 0 AN: 45619

GnomAD4 genome AF: 0.00000894 AC: 1 AN: 111888 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34068

African (AFR) AF: 0.00 AC: 0 AN: 30736

American (AMR) AF: 0.00 AC: 0 AN: 10511

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3599

South Asian (SAS) AF: 0.00 AC: 0 AN: 2700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53202

Other (OTH) AF: 0.00 AC: 0 AN: 1498

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.090	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.66		Gain of disorder (P = 0.0818)
MVP		0.88
MPC		0.57
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.89
gMVP		0.88
Mutation Taster		=68/32	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: rs1931839771; hg19: chrX-15790633;