rs770395993

Variant names:

• chr15-63326313-G-C
• rs770395993
• NM_001218.5:c.1037C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-63326313-G-C
• chr15-63326313-G-T

Variant summary

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

The NM_001218.5(CA12):​c.1037C>G​(p.Thr346Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CA12 NM_001218.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.899

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=0.053625762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA12	NM_001218.5	c.1037C>G	p.Thr346Ser	missense_variant	Exon 11 of 11	ENST00000178638.8	NP_001209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA12	ENST00000178638.8	c.1037C>G	p.Thr346Ser	missense_variant	Exon 11 of 11	1	NM_001218.5	ENSP00000178638.3
CA12	ENST00000344366.7	c.1004C>G	p.Thr335Ser	missense_variant	Exon 10 of 10	1		ENSP00000343088.3
CA12	ENST00000422263.2	c.824C>G	p.Thr275Ser	missense_variant	Exon 9 of 9	2		ENSP00000403028.2
CA12	ENST00000560666.1	n.247C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.1
DANN	Benign	0.85
DEOGEN2	Benign	0.10	T;.;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.054	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.37	N;N;N
REVEL	Benign	0.084
Sift	Benign	0.077	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		0.094	B;B;B
Vest4		0.048
MutPred		0.16		Gain of disorder (P = 0.0519);.;.;
MVP		0.62
MPC		0.14
ClinPred		0.064	T
GERP RS		2.2
Varity_R		0.043
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs770395993; hg19: chr15-63618512;