Variant 1-8949347-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000377443.7(CA6):c.164C>T(p.Thr55Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,611,070 control chromosomes in the GnomAD database, including 117,752 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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.

Frequency

Genomes: 𝑓 0.32 ( 9002 hom., cov: 33)

Exomes 𝑓: 0.38 ( 108750 hom. )

Consequence

CA6
ENST00000377443.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.241

Variant links:

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]

CA6 links:

CA6 (HGNC:):

CA6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.671118E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CA6	NM_001215.4 linkuse as main transcript	c.164C>T	p.Thr55Met	missense_variant	2/8	ENST00000377443.7	NP_001206.2	P23280-1B4DUH8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA6	ENST00000377443.7 linkuse as main transcript	c.164C>T	p.Thr55Met	missense_variant	2/8	1	NM_001215.4	ENSP00000366662.2		P23280-1
CA6	ENST00000480186.7 linkuse as main transcript	c.164C>T	p.Thr55Met	missense_variant	2/3	2		ENSP00000435280.1		Q8N4G4

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48697

AN:

151908

Hom.:

9004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.534

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.367

GnomAD3 exomes

AF:

0.357

AC:

89130

AN:

249486

Hom.:

17108

AF XY:

0.361

AC XY:

48773

AN XY:

134926

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.319

Gnomad ASJ exome

AF:

0.507

Gnomad EAS exome

AF:

0.249

Gnomad SAS exome

AF:

0.280

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.380

AC:

554810

AN:

1459044

Hom.:

108750

Cov.:

AF XY:

0.378

AC XY:

274518

AN XY:

725892

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.323

Gnomad4 ASJ exome

AF:

0.507

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.459

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.377

GnomAD4 genome

AF:

0.320

AC:

48702

AN:

152026

Hom.:

9002

Cov.:

AF XY:

0.323

AC XY:

24000

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.348

Gnomad4 ASJ

AF:

0.525

Gnomad4 EAS

AF:

0.254

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.467

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.367

Alfa

AF:

0.387

Hom.:

28081

Bravo

AF:

0.307

TwinsUK

AF:

0.395

AC:

1465

ALSPAC

AF:

0.395

AC:

1521

ESP6500AA

AF:

0.144

AC:

635

ESP6500EA

AF:

0.414

AC:

3559

ExAC

AF:

0.354

AC:

42929

Asia WGS

AF:

0.294

AC:

1022

AN:

3478

EpiCase

AF:

0.408

EpiControl

AF:

0.419

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

6.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

.;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.40

T;T;T;T

MetaRNN

Benign

0.00077

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;.;L;L

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.27

N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.10

T;D;T;D

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.99

.;.;D;.

Vest4

0.073, 0.098, 0.10

MPC

0.55

ClinPred

0.066

GERP RS

-7.7

Varity_R

0.037

gMVP

0.49

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over