17-52157734-C-A

Variant names:

• chr17-52157734-C-A
• NM_020178.5:c.53G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020178.5(CA10):​c.53G>T​(p.Cys18Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CA10 NM_020178.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.80

Genes affected

CA10 (HGNC:1369): (carbonic anhydrase 10) This gene encodes a protein that belongs to the carbonic anhydrase family of zinc metalloenzymes, which catalyze the reversible hydration of carbon dioxide in various biological processes. The protein encoded by this gene is an acatalytic member of the alpha-carbonic anhydrase subgroup, and it is thought to play a role in the central nervous system, especially in brain development. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA10	NM_020178.5	c.53G>T	p.Cys18Phe	missense_variant	Exon 1 of 9	ENST00000451037.7	NP_064563.1
CA10	NM_001082533.1	c.53G>T	p.Cys18Phe	missense_variant	Exon 2 of 10		NP_001076002.1
CA10	NM_001082534.2	c.53G>T	p.Cys18Phe	missense_variant	Exon 2 of 10		NP_001076003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA10	ENST00000451037.7	c.53G>T	p.Cys18Phe	missense_variant	Exon 1 of 9	1	NM_020178.5	ENSP00000405388.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.53G>T (p.C18F) alteration is located in exon 2 (coding exon 1) of the CA10 gene. This alteration results from a G to T substitution at nucleotide position 53, causing the cysteine (C) at amino acid position 18 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.038	T;T;T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.67	.;.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;N;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.4	N;N;N;.
REVEL	Uncertain	0.37
Sift	Benign	0.082	T;T;T;.
Sift4G	Benign	0.39	T;T;T;T
Polyphen		0.86	P;P;P;.
Vest4		0.83
MutPred		0.68		Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);
MVP		0.89
MPC		0.75
ClinPred		0.50	D
GERP RS		5.3
Varity_R		0.32
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-50235094;