1-8949392-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001215.4(CA6):c.209G>C(p.Gly70Ala) variant causes a missense change. The variant allele was found at a frequency of 0.096 in 1,610,582 control chromosomes in the GnomAD database, including 8,499 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. G70G) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.073 (551 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7948 hom.)
• Consequence: CA6 NM_001215.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025099218).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA6	NM_001215.4	c.209G>C	p.Gly70Ala	missense_variant	2/8	ENST00000377443.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA6	ENST00000377443.7	c.209G>C	p.Gly70Ala	missense_variant	2/8	1	NM_001215.4	P2

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11126 AN: 152078 Hom.: 555 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0837

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.0688

GnomAD3 exomes AF: 0.0931 AC: 23267 AN: 250018 Hom.: 1407 AF XY: 0.0990 AC XY: 13391 AN XY: 135210

Gnomad AFR exome AF: 0.0166

Gnomad AMR exome AF: 0.0356

Gnomad ASJ exome AF: 0.0973

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.0775

Gnomad NFE exome AF: 0.0917

Gnomad OTH exome AF: 0.0922

GnomAD4 exome AF: 0.0984 AC: 143505 AN: 1458386 Hom.: 7948 Cov.: 33 AF XY: 0.101 AC XY: 73058 AN XY: 725648

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.0371

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.0768

Gnomad4 NFE exome AF: 0.0959

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0731 AC: 11120 AN: 152196 Hom.: 551 Cov.: 32 AF XY: 0.0738 AC XY: 5494 AN XY: 74434

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.0961

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0903 Hom.: 552

Bravo AF: 0.0680

TwinsUK AF: 0.0992 AC: 368

ALSPAC AF: 0.106 AC: 407

ESP6500AA AF: 0.0209 AC: 92

ESP6500EA AF: 0.0953 AC: 820

ExAC AF: 0.0924 AC: 11212

Asia WGS AF: 0.146 AC: 505 AN: 3478

EpiCase AF: 0.0999

EpiControl AF: 0.0916

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T;T;T
MetaRNN	Benign	0.0025	T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.032	P;P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.2	D;D;D
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.14	T;D;D
Polyphen		1.0	.;D;.
Vest4		0.23
MPC		0.67
ClinPred		0.051	T
GERP RS		3.4
Varity_R		0.28
gMVP		0.70

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: rs2274329; hg19: chr1-9009451; COSMIC: COSV66261780;