chr16-69115261-G-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_001199280.2(HAS3):c.1657G>C(p.Val553Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000231 in 1,517,974 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 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
HAS3
NM_001199280.2 missense
NM_001199280.2 missense
Scores
2
5
10
Clinical Significance
Conservation
PhyloP100: 6.24
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, HAS3
BP4
?
Computational evidence support a benign effect (MetaRNN=0.04705724).
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HAS3 | NM_001199280.2 | c.1657G>C | p.Val553Leu | missense_variant | 4/4 | ENST00000569188.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HAS3 | ENST00000569188.6 | c.1657G>C | p.Val553Leu | missense_variant | 4/4 | 2 | NM_001199280.2 | P1 | |
HAS3 | ENST00000306560.1 | c.1657G>C | p.Val553Leu | missense_variant | 4/4 | 1 | P1 | ||
HAS3 | ENST00000219322.7 | c.738+1719G>C | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152132Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000227 AC: 4AN: 176394Hom.: 0 AF XY: 0.0000215 AC XY: 2AN XY: 93106
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GnomAD4 exome AF: 0.0000198 AC: 27AN: 1365842Hom.: 0 Cov.: 34 AF XY: 0.0000254 AC XY: 17AN XY: 669106
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74290
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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 | Jan 31, 2022 | The c.1657G>C (p.V553L) alteration is located in exon 4 (coding exon 3) of the HAS3 gene. This alteration results from a G to C substitution at nucleotide position 1657, causing the valine (V) at amino acid position 553 to be replaced by a leucine (L). 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
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
B;B
Vest4
MutPred
Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP
MPC
0.83
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at