17-51747671-A-T

Variant names:

• chr17-51747671-A-T
• rs763972021
• NM_020178.5:c.427T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020178.5(CA10):​c.427T>A​(p.Ser143Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CA10 NM_020178.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.29
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020178.5. 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
	CA10	NM_020178.5	MANE Select	c.427T>A	p.Ser143Thr	missense	Exon 4 of 9	NP_064563.1	A0A384MTY8
	CA10	NM_001082533.1		c.427T>A	p.Ser143Thr	missense	Exon 5 of 10	NP_001076002.1	Q9NS85-1
	CA10	NM_001082534.2		c.427T>A	p.Ser143Thr	missense	Exon 5 of 10	NP_001076003.1	A0A384MTY8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA10	ENST00000451037.7	TSL:1 MANE Select	c.427T>A	p.Ser143Thr	missense	Exon 4 of 9	ENSP00000405388.2	Q9NS85-1
	CA10	ENST00000285273.8	TSL:1	c.427T>A	p.Ser143Thr	missense	Exon 5 of 10	ENSP00000285273.4	Q9NS85-1
	CA10	ENST00000442502.6	TSL:1	c.427T>A	p.Ser143Thr	missense	Exon 5 of 10	ENSP00000390666.2	Q9NS85-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152082 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251140 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461770 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727184

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152082 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74284

African (AFR) AF: 0.0000241 AC: 1 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

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	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		9.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.8	D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.95
MVP		0.92
MPC		1.0
ClinPred		1.0	D
GERP RS		5.7
PromoterAI		0.028	Neutral
Varity_R		0.65
gMVP		0.91

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

Other links and lift over

dbSNP: rs763972021; hg19: chr17-49825031;