NM_001215.4:c.176A>G

Variant names:

• chr1-8949359-A-G
• rs753185301
• NM_001215.4:c.176A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001215.4(CA6):​c.176A>G​(p.Tyr59Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,613,460 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: CA6 NM_001215.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13
• Publications: 1 publications found

Genes affected

CA6 (HGNC:1380): (carbonic anhydrase 6) The protein encoded by this gene is one of several isozymes of carbonic anhydrase. This protein is found only in salivary glands and saliva and protein may play a role in the reversible hydratation of carbon dioxide though its function in saliva is unknown. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001215.4. 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
	CA6	NM_001215.4	MANE Select	c.176A>G	p.Tyr59Cys	missense	Exon 2 of 8	NP_001206.2	P23280-1
	CA6	NM_001270500.2		c.176A>G	p.Tyr59Cys	missense	Exon 2 of 8	NP_001257429.1	P23280-2
	CA6	NM_001270501.2		c.79+3394A>G		intron	N/A	NP_001257430.1	P23280-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA6	ENST00000377443.7	TSL:1 MANE Select	c.176A>G	p.Tyr59Cys	missense	Exon 2 of 8	ENSP00000366662.2	P23280-1
	CA6	ENST00000377436.6	TSL:1	c.176A>G	p.Tyr59Cys	missense	Exon 2 of 8	ENSP00000366654.3	P23280-2
	CA6	ENST00000480186.7	TSL:2	c.176A>G	p.Tyr59Cys	missense	Exon 2 of 3	ENSP00000435280.1	Q8N4G4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152156 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

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: 0.0000279 AC: 7 AN: 250706 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000122 AC: 178 AN: 1461186 Hom.: 1 Cov.: 33 AF XY: 0.000117 AC XY: 85 AN XY: 726932

African (AFR) AF: 0.0000898 AC: 3 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39676

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

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

European-Non Finnish (NFE) AF: 0.000135 AC: 150 AN: 1111592

Other (OTH) AF: 0.000232 AC: 14 AN: 60372

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152274 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41528

American (AMR) AF: 0.00 AC: 0 AN: 15298

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

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000141 Hom.: 0

Bravo AF: 0.000106

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	Uncertain	0.50
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.15
Eigen_PC	Benign	-0.00089
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.1
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.68		Loss of sheet (P = 0.0817)
MVP		0.87
MPC		0.71
ClinPred		0.94	D
GERP RS		1.1
Varity_R		0.74
gMVP		0.78
Mutation Taster		=80/20	polymorphism

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: rs753185301; hg19: chr1-9009418; COSMIC: COSV101077618;