chr16-69109850-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001199280.2(HAS3):c.455G>A(p.Arg152His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000707 in 1,613,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
HAS3
NM_001199280.2 missense
NM_001199280.2 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 2.33
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, HAS3
BP4
?
Computational evidence support a benign effect (MetaRNN=0.10140306).
BS2
?
High AC in GnomAd at 46 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HAS3 | NM_001199280.2 | c.455G>A | p.Arg152His | missense_variant | 2/4 | ENST00000569188.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HAS3 | ENST00000569188.6 | c.455G>A | p.Arg152His | missense_variant | 2/4 | 2 | NM_001199280.2 | P1 | |
HAS3 | ENST00000306560.1 | c.455G>A | p.Arg152His | missense_variant | 2/4 | 1 | P1 | ||
HAS3 | ENST00000219322.7 | c.455G>A | p.Arg152His | missense_variant | 2/4 | 1 | |||
HAS3 | ENST00000566118.5 | c.455G>A | p.Arg152His | missense_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000302 AC: 46AN: 152240Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
46
AN:
152240
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000999 AC: 25AN: 250360Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135518
GnomAD3 exomes
AF:
AC:
25
AN:
250360
Hom.:
AF XY:
AC XY:
10
AN XY:
135518
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000465 AC: 68AN: 1460994Hom.: 0 Cov.: 34 AF XY: 0.0000371 AC XY: 27AN XY: 726862
GnomAD4 exome
AF:
AC:
68
AN:
1460994
Hom.:
Cov.:
34
AF XY:
AC XY:
27
AN XY:
726862
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000302 AC: 46AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23AN XY: 74506
GnomAD4 genome
?
AF:
AC:
46
AN:
152358
Hom.:
Cov.:
33
AF XY:
AC XY:
23
AN XY:
74506
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
4
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
14
EpiCase
AF:
EpiControl
AF:
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 | Aug 02, 2023 | The c.455G>A (p.R152H) 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 455, causing the arginine (R) at amino acid position 152 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
Sift
Benign
T;D;D;T
Sift4G
Uncertain
D;D;D;D
Polyphen
P;D;.;P
Vest4
MVP
MPC
1.8
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at