rs2030900477

Variant names:

• chr19-48638140-A-C
• rs2030900477
• NM_001217.5:c.966T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001217.5(CA11):​c.966T>G​(p.Asp322Glu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CA11 NM_001217.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0450
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24602494).

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.966T>G	p.Asp322Glu	missense	Exon 9 of 9	NP_001208.2
	SEC1P	NR_004401.2		n.102A>C		non_coding_transcript_exon	Exon 1 of 5
	CA11	NR_136241.2		n.2169T>G		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.966T>G	p.Asp322Glu	missense	Exon 9 of 9	ENSP00000084798.3	O75493
	SEC1P	ENST00000474419.5	TSL:1	n.70A>C		non_coding_transcript_exon	Exon 1 of 4
	SEC1P	ENST00000483163.1	TSL:1	n.70A>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000176 AC: 2 AN: 1138262 Hom.: 0 Cov.: 29 AF XY: 0.00000181 AC XY: 1 AN XY: 552786

African (AFR) AF: 0.00 AC: 0 AN: 23626

American (AMR) AF: 0.000142 AC: 2 AN: 14124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12836

East Asian (EAS) AF: 0.00 AC: 0 AN: 26742

South Asian (SAS) AF: 0.00 AC: 0 AN: 54474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 924086

Other (OTH) AF: 0.00 AC: 0 AN: 43148

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.15
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.045
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.010	N
REVEL	Benign	0.28
Sift	Benign	0.062	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.90	P
Vest4		0.34
MutPred		0.33		Loss of sheet (P = 0.0043)
MVP		0.71
MPC		0.76
ClinPred		0.50	T
GERP RS		-0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.69
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2030900477; hg19: chr19-49141397;