19-48638131-GG-CC

Variant names:

• chr19-48638131-GG-CC
• NM_001217.5:c.974_975delCCinsGG
• CA11 p.Pro325Arg

Variant summary

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

The NM_001217.5(CA11):​c.974_975delCCinsGG​(p.Pro325Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P325L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 28)
• Consequence: CA11 NM_001217.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

Genes affected

CA11 (HGNC:1370): (carbonic anhydrase 11) 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. CA XI is likely a secreted protein, however, radical changes at active site residues completely conserved in CA isozymes with catalytic activity, make it unlikely that it has carbonic anhydrase activity. It shares properties in common with two other acatalytic CA isoforms, CA VIII and CA X. CA XI is most abundantly expressed in brain, and may play a general role in the central nervous system. [provided by RefSeq, Jul 2008]

SEC1P (HGNC:):

SEC1P (HGNC:44149): (secretory blood group 1, pseudogene) Predicted to enable galactoside 2-alpha-L-fucosyltransferase activity. Predicted to act upstream of or within protein glycosylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001217.5. 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
	CA11	NM_001217.5	MANE Select	c.974_975delCCinsGG	p.Pro325Arg	missense	N/A	NP_001208.2
	SEC1P	NR_004401.2		n.93_94delGGinsCC		non_coding_transcript_exon	Exon 1 of 5
	CA11	NR_136241.2		n.2177_2178delCCinsGG		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA11	ENST00000084798.9	TSL:1 MANE Select	c.974_975delCCinsGG	p.Pro325Arg	missense	N/A	ENSP00000084798.3	O75493
	SEC1P	ENST00000474419.5	TSL:1	n.61_62delGGinsCC		non_coding_transcript_exon	Exon 1 of 4
	SEC1P	ENST00000483163.1	TSL:1	n.61_62delGGinsCC		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 28

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-49141388;