chr17-51635938-C-T

Position:

• chr17-51635938-C-T

Variant summary

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

The NM_020178.5(CA10):​c.706G>A​(p.Asp236Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,388 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CA10 NM_020178.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.75

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/exons	MANE	Protein	UniProt
CA10	NM_020178.5	c.706G>A	p.Asp236Asn	missense_variant	7/9	ENST00000451037.7	NP_064563.1
CA10	NM_001082533.1	c.706G>A	p.Asp236Asn	missense_variant	8/10		NP_001076002.1
CA10	NM_001082534.2	c.706G>A	p.Asp236Asn	missense_variant	8/10		NP_001076003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA10	ENST00000451037.7	c.706G>A	p.Asp236Asn	missense_variant	7/9	1	NM_020178.5	ENSP00000405388	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1457388 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725260

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

research

Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo

Feb 08, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.056	.;T;T;T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;.;.;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.47	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.23	.;N;N;N;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.3	.;N;N;N;.
REVEL	Benign	0.15
Sift	Uncertain	0.0060	.;D;D;D;.
Sift4G	Benign	0.33	T;T;T;T;T
Polyphen		0.44	.;B;B;B;.
Vest4		0.54
MVP		0.42
MPC		0.44
ClinPred		0.92	D
GERP RS		6.2
Varity_R		0.24
gMVP		0.50

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

LitVar

Other links and lift over

dbSNP: rs1046164022; hg19: chr17-49713299; COSMIC: COSV53350094;