15-63327183-CCA-CCACA

Variant names:

• chr15-63327183-C-CCA
• rs757974800
• NM_001218.5:c.956_957dupTG

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001218.5(CA12):​c.956_957dupTG​(p.Val320TrpfsTer124) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.101 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA12	NM_001218.5	c.956_957dupTG	p.Val320TrpfsTer124	frameshift_variant	Exon 10 of 11	ENST00000178638.8	NP_001209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA12	ENST00000178638.8	c.956_957dupTG	p.Val320TrpfsTer124	frameshift_variant	Exon 10 of 11	1	NM_001218.5	ENSP00000178638.3
CA12	ENST00000344366.7	c.923_924dupTG	p.Val309TrpfsTer124	frameshift_variant	Exon 9 of 10	1		ENSP00000343088.3
CA12	ENST00000422263.2	c.743_744dupTG	p.Val249TrpfsTer124	frameshift_variant	Exon 8 of 9	2		ENSP00000403028.2
CA12	ENST00000560666.1	n.166_167dupTG		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs757974800; hg19: chr15-63619382;