NM_020178.5:c.269G>A

Variant names:

• chr17-51931000-C-T
• rs769454483
• NM_020178.5:c.269G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_020178.5(CA10):​c.269G>A​(p.Gly90Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: CA10 NM_020178.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.64
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32319462).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

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.269G>A	p.Gly90Glu	missense	Exon 3 of 9	NP_064563.1	A0A384MTY8
	CA10	NM_001082533.1		c.269G>A	p.Gly90Glu	missense	Exon 4 of 10	NP_001076002.1	Q9NS85-1
	CA10	NM_001082534.2		c.269G>A	p.Gly90Glu	missense	Exon 4 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.269G>A	p.Gly90Glu	missense	Exon 3 of 9	ENSP00000405388.2	Q9NS85-1
	CA10	ENST00000285273.8	TSL:1	c.269G>A	p.Gly90Glu	missense	Exon 4 of 10	ENSP00000285273.4	Q9NS85-1
	CA10	ENST00000442502.6	TSL:1	c.269G>A	p.Gly90Glu	missense	Exon 4 of 10	ENSP00000390666.2	Q9NS85-1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151936 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250846 AF XY: 0.0000369

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461074 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726842

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111472

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151936 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74176

African (AFR) AF: 0.00 AC: 0 AN: 41360

American (AMR) AF: 0.0000656 AC: 1 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000330 AC: 4

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	0.70
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.13	T
Sift4G	Benign	0.24	T
Polyphen		0.99	D
Vest4		0.81
MVP		0.30
MPC		1.3
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.29
gMVP		0.71
Mutation Taster		=44/56	disease causing

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: rs769454483; hg19: chr17-50008360; COSMIC: COSV105131627; COSMIC: COSV105131627;