Menu
GeneBe

19-51713752-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001297436.2(HAS1):c.1409G>A(p.Gly470Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,606,558 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

HAS1
NM_001297436.2 missense

Scores

2
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68
Variant links:
Genes affected
HAS1 (HGNC:4818): (hyaluronan synthase 1) Hyaluronan or hyaluronic acid (HA) is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. HA is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded through pore-like structures into the extracellular space. It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. HA is actively produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of HA are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of HA with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of HA receptors has been correlated with tumor metastasis. HAS1 is a member of the newly identified vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to the hasA gene product of Streptococcus pyogenes, a glycosaminoglycan synthetase (DG42) from Xenopus laevis, and a recently described murine hyaluronan synthase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HAS1NM_001297436.2 linkuse as main transcriptc.1409G>A p.Gly470Asp missense_variant 5/5 ENST00000540069.7
HAS1NM_001523.4 linkuse as main transcriptc.1412G>A p.Gly471Asp missense_variant 5/5
HAS1XM_011526884.3 linkuse as main transcriptc.*292G>A 3_prime_UTR_variant 4/4
HAS1XM_047438719.1 linkuse as main transcriptc.*292G>A 3_prime_UTR_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HAS1ENST00000540069.7 linkuse as main transcriptc.1409G>A p.Gly470Asp missense_variant 5/51 NM_001297436.2 A1
HAS1ENST00000601714.5 linkuse as main transcriptc.1433G>A p.Gly478Asp missense_variant 4/41
HAS1ENST00000222115.5 linkuse as main transcriptc.1412G>A p.Gly471Asp missense_variant 5/51 P4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152230
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000265
AC:
6
AN:
226234
Hom.:
0
AF XY:
0.0000242
AC XY:
3
AN XY:
124010
show subpopulations
Gnomad AFR exome
AF:
0.0000748
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000688
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000302
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000172
AC:
25
AN:
1454328
Hom.:
0
Cov.:
32
AF XY:
0.0000194
AC XY:
14
AN XY:
723168
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.0000113

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 submitterclinical testingAmbry GeneticsJul 08, 2022The c.1412G>A (p.G471D) alteration is located in exon 5 (coding exon 5) of the HAS1 gene. This alteration results from a G to A substitution at nucleotide position 1412, causing the glycine (G) at amino acid position 471 to be replaced by an aspartic acid (D). 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
Pathogenic
0.99
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.26
Cadd
Pathogenic
29
Dann
Uncertain
1.0
Eigen
Uncertain
0.28
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.58
D;D;D
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.81
D
Sift4G
Benign
0.33
T;T;T
Polyphen
0.97, 0.98
.;D;D
Vest4
0.71
MutPred
0.48
.;Loss of ubiquitination at K476 (P = 0.0982);.;
MVP
0.49
MPC
0.38
ClinPred
0.45
T
GERP RS
3.1
Varity_R
0.41
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.

Other links and lift over

dbSNP: rs1196353914; hg19: chr19-52217005; API