rs3829078

Variant names:

• chr9-35679254-A-G
• rs3829078
• NM_001216.3:c.977A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-35679254-A-G
• chr9-35679254-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001216.3(CA9):​c.977A>G​(p.Gln326Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 1,614,030 control chromosomes in the GnomAD database, including 9,096 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.075 (507 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8589 hom.)
• Consequence: CA9 NM_001216.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 35 publications found

Genes affected

CA9 (HGNC:1383): (carbonic anhydrase 9) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA IX is a transmembrane protein and is one of only two tumor-associated carbonic anhydrase isoenzymes known. It is expressed in all clear-cell renal cell carcinoma, but is not detected in normal kidney or most other normal tissues. It may be involved in cell proliferation and transformation. This gene was mapped to 17q21.2 by fluorescence in situ hybridization, however, radiation hybrid mapping localized it to 9p13-p12. [provided by RefSeq, Jun 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033312142).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001216.3. 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
	CA9	NM_001216.3	MANE Select	c.977A>G	p.Gln326Arg	missense	Exon 7 of 11	NP_001207.2	Q16790

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA9	ENST00000378357.9	TSL:1 MANE Select	c.977A>G	p.Gln326Arg	missense	Exon 7 of 11	ENSP00000367608.4	Q16790
	CA9	ENST00000903367.1		c.1139A>G	p.Gln380Arg	missense	Exon 8 of 12	ENSP00000573426.1
	CA9	ENST00000903366.1		c.947A>G	p.Gln316Arg	missense	Exon 6 of 10	ENSP00000573425.1

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11408 AN: 152110 Hom.: 506 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.0634

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0822

GnomAD2 exomes AF: 0.0817 AC: 20544 AN: 251462 AF XY: 0.0817

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.0756

Gnomad ASJ exome AF: 0.0497

Gnomad EAS exome AF: 0.0346

Gnomad FIN exome AF: 0.0616

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.0784

GnomAD4 exome AF: 0.102 AC: 149835 AN: 1461802 Hom.: 8589 Cov.: 32 AF XY: 0.102 AC XY: 73834 AN XY: 727214

African (AFR) AF: 0.0231 AC: 775 AN: 33480

American (AMR) AF: 0.0746 AC: 3335 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 1289 AN: 26136

East Asian (EAS) AF: 0.0244 AC: 968 AN: 39696

South Asian (SAS) AF: 0.0607 AC: 5233 AN: 86258

European-Finnish (FIN) AF: 0.0614 AC: 3278 AN: 53420

Middle Eastern (MID) AF: 0.0487 AC: 281 AN: 5766

European-Non Finnish (NFE) AF: 0.116 AC: 129124 AN: 1111940

Other (OTH) AF: 0.0919 AC: 5552 AN: 60394

GnomAD4 genome AF: 0.0750 AC: 11418 AN: 152228 Hom.: 507 Cov.: 32 AF XY: 0.0720 AC XY: 5357 AN XY: 74410

African (AFR) AF: 0.0249 AC: 1034 AN: 41560

American (AMR) AF: 0.0805 AC: 1229 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3472

East Asian (EAS) AF: 0.0307 AC: 159 AN: 5182

South Asian (SAS) AF: 0.0541 AC: 261 AN: 4824

European-Finnish (FIN) AF: 0.0634 AC: 672 AN: 10600

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7643 AN: 68000

Other (OTH) AF: 0.0842 AC: 178 AN: 2114

Alfa AF: 0.100 Hom.: 3072

Bravo AF: 0.0757

TwinsUK AF: 0.121 AC: 448

ALSPAC AF: 0.111 AC: 429

ESP6500AA AF: 0.0300 AC: 132

ESP6500EA AF: 0.113 AC: 969

ExAC AF: 0.0820 AC: 9962

Asia WGS AF: 0.0620 AC: 215 AN: 3478

EpiCase AF: 0.110

EpiControl AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.66
DEOGEN2	Benign	0.064	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.0	N
PhyloP100		1.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.043
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.052
MPC		0.16
ClinPred		0.00019	T
GERP RS		2.5
Varity_R		0.27
gMVP		0.72
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3829078; hg19: chr9-35679251; COSMIC: COSV61405203; COSMIC: COSV61405203;