Variant 16-69109609-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001199280.2(HAS3):c.214C>T(p.Arg72Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000697 in 1,612,182 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 1 hom. )

Consequence

HAS3
NM_001199280.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.533

Variant links:

Genes affected

HAS3 (HGNC:4820): (hyaluronan synthase 3) The protein encoded by this gene is involved in the synthesis of the unbranched glycosaminoglycan hyaluronan, or hyaluronic acid, which is a major constituent of the extracellular matrix. This gene is a member of the NODC/HAS gene family. Compared to the proteins encoded by other members of this gene family, this protein appears to be more of a regulator of hyaluronan synthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

HAS3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, HAS3

BP4

Computational evidence support a benign effect (MetaRNN=0.00464952).

BP6

Variant 16-69109609-C-T is Benign according to our data. Variant chr16-69109609-C-T is described in ClinVar as [Benign]. Clinvar id is 709923.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 526 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAS3	NM_001199280.2 linkuse as main transcript	c.214C>T	p.Arg72Cys	missense_variant	2/4	ENST00000569188.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAS3	ENST00000569188.6 linkuse as main transcript	c.214C>T	p.Arg72Cys	missense_variant	2/4	2	NM_001199280.2	P1	O00219-1
HAS3	ENST00000306560.1 linkuse as main transcript	c.214C>T	p.Arg72Cys	missense_variant	2/4	1		P1	O00219-1
HAS3	ENST00000219322.7 linkuse as main transcript	c.214C>T	p.Arg72Cys	missense_variant	2/4	1			O00219-2
HAS3	ENST00000566118.5 linkuse as main transcript	c.214C>T	p.Arg72Cys	missense_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

526

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

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:

0.0000441

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.000915

AC:

228

AN:

249128

Hom.:

AF XY:

0.000638

AC XY:

AN XY:

134880

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000799

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000410

AC:

598

AN:

1459840

Hom.:

Cov.:

AF XY:

0.000368

AC XY:

267

AN XY:

726320

show subpopulations

Gnomad4 AFR exome

AF:

0.0139

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152342

Hom.:

Cov.:

AF XY:

0.00338

AC XY:

252

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000997

Hom.:

Bravo

AF:

0.00424

ESP6500AA

AF:

0.0136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00106

AC:

129

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.79

D;.;T;D

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.14

MetaRNN

Benign

0.0046

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;.;L

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.2

N;N;N;N

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Uncertain

0.022

D;D;D;D

Polyphen

0.86

P;P;.;P

Vest4

0.33

MVP

0.16

MPC

1.4

ClinPred

0.019

GERP RS

3.4

Varity_R

0.097

gMVP

0.77

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over