Variant 16-69109825-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2

The NM_001199280.2(HAS3):c.430G>A(p.Glu144Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,460,380 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

HAS3
NM_001199280.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.33

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 Uncertain_significance. Variant got 1 ACMG points.

PP2

Missense variant where missense usually causes diseases, HAS3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAS3	NM_001199280.2 linkuse as main transcript	c.430G>A	p.Glu144Lys	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.430G>A	p.Glu144Lys	missense_variant	2/4	2	NM_001199280.2	P1	O00219-1
HAS3	ENST00000306560.1 linkuse as main transcript	c.430G>A	p.Glu144Lys	missense_variant	2/4	1		P1	O00219-1
HAS3	ENST00000219322.7 linkuse as main transcript	c.430G>A	p.Glu144Lys	missense_variant	2/4	1			O00219-2
HAS3	ENST00000566118.5 linkuse as main transcript	c.430G>A	p.Glu144Lys	missense_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249790

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1460380

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.430G>A (p.E144K) alteration is located in exon 2 (coding exon 1) of the HAS3 gene. This alteration results from a G to A substitution at nucleotide position 430, causing the glutamic acid (E) at amino acid position 144 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Uncertain

0.010

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

M_CAP

Uncertain

0.27

MetaRNN

Uncertain

0.65

D;D;D;D

MetaSVM

Uncertain

0.044

MutationAssessor

Benign

1.3

L;L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.7

N;N;N;N

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.070

T;T;T;T

Polyphen

0.91

P;P;.;P

Vest4

0.44

MutPred

0.51

Gain of ubiquitination at E144 (P = 0.0289);Gain of ubiquitination at E144 (P = 0.0289);Gain of ubiquitination at E144 (P = 0.0289);Gain of ubiquitination at E144 (P = 0.0289);

MVP

0.73

MPC

1.0

ClinPred

0.78

GERP RS

5.6

Varity_R

0.27

gMVP

0.68

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