rs190933299

Variant names:

• chr8-85448118-A-G
• rs190933299
• NM_005181.4:c.748A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005181.4(CA3):​c.748A>G​(p.Ile250Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: CA3 NM_005181.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.170
• Publications: 1 publications found

Genes affected

CA3 (HGNC:1374): (carbonic anhydrase 3) Carbonic anhydrase III (CAIII) is a member of a multigene family (at least six separate genes are known) that encodes carbonic anhydrase isozymes. These carbonic anhydrases are a class of metalloenzymes that catalyze the reversible hydration of carbon dioxide and are differentially expressed in a number of cell types. The expression of the CA3 gene is strictly tissue specific and present at high levels in skeletal muscle and much lower levels in cardiac and smooth muscle. A proportion of carriers of Duchenne muscle dystrophy have a higher CA3 level than normal. The gene spans 10.3 kb and contains seven exons and six introns. [provided by RefSeq, Oct 2008]

CA3-AS1 (HGNC:51657): (CA3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010671437).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005181.4. 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
	CA3	NM_005181.4	MANE Select	c.748A>G	p.Ile250Val	missense	Exon 7 of 7	NP_005172.1	P07451
	CA3-AS1	NR_121630.1		n.401-5881T>C		intron	N/A
	CA3-AS1	NR_121631.1		n.173-5881T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA3	ENST00000285381.3	TSL:1 MANE Select	c.748A>G	p.Ile250Val	missense	Exon 7 of 7	ENSP00000285381.2	P07451
	CA3	ENST00000967721.1		c.673A>G	p.Ile225Val	missense	Exon 7 of 7	ENSP00000637780.1
	CA3	ENST00000967722.1		c.592A>G	p.Ile198Val	missense	Exon 6 of 6	ENSP00000637781.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000719 AC: 18 AN: 250256 AF XY: 0.0000666

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000335 AC: 49 AN: 1461136 Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25 AN XY: 726836

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000897 AC: 4 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39690

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 85982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111690

Other (OTH) AF: 0.000116 AC: 7 AN: 60376

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74486

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.0000847 Hom.: 0

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.0000594

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	Benign	0.076
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.4
DANN	Benign	0.90
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.075	N
PhyloP100		-0.17
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.28
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.046	D
Polyphen		0.0	B
Vest4		0.040
MVP		0.25
MPC		0.13
ClinPred		0.029	T
GERP RS		-12
Varity_R		0.16
gMVP		0.53
Mutation Taster		=90/10	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

dbSNP: rs190933299; hg19: chr8-86360347;