15-63328115-G-T

Variant names:

• chr15-63328115-G-T
• rs747884567
• NM_001218.5:c.890C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001218.5(CA12):​c.890C>A​(p.Ala297Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CA12 NM_001218.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

CA12 (HGNC:1371): (carbonic anhydrase 12) 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. This gene product is a type I membrane protein that is highly expressed in normal tissues, such as kidney, colon and pancreas, and has been found to be overexpressed in 10% of clear cell renal carcinomas. Three transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2014]

LOC124903506 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054767072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA12	NM_001218.5	c.890C>A	p.Ala297Glu	missense_variant	Exon 9 of 11	ENST00000178638.8	NP_001209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA12	ENST00000178638.8	c.890C>A	p.Ala297Glu	missense_variant	Exon 9 of 11	1	NM_001218.5	ENSP00000178638.3
CA12	ENST00000344366.7	c.875-882C>A		intron_variant	Intron 8 of 9	1		ENSP00000343088.3
CA12	ENST00000422263.2	c.695-882C>A		intron_variant	Intron 7 of 8	2		ENSP00000403028.2
CA12	ENST00000560666.1	n.118-882C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461676 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.21
DANN	Benign	0.28
DEOGEN2	Benign	0.096	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.054
Sift	Benign	0.55	T
Sift4G	Benign	0.48	T
Polyphen		0.072	B
Vest4		0.21
MutPred		0.46		Gain of solvent accessibility (P = 0.0456);
MVP		0.25
MPC		0.19
ClinPred		0.046	T
GERP RS		-8.0
Varity_R		0.069
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs747884567; hg19: chr15-63620314; COSMIC: COSV51605913;