chr16-69109609-C-T
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
NM_001199280.2 missense
Scores
5
11
Clinical Significance
Conservation
PhyloP100: 0.533
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 -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 | 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 | c.214C>T | p.Arg72Cys | missense_variant | 2/4 | 2 | NM_001199280.2 | P1 | |
HAS3 | ENST00000306560.1 | c.214C>T | p.Arg72Cys | missense_variant | 2/4 | 1 | P1 | ||
HAS3 | ENST00000219322.7 | c.214C>T | p.Arg72Cys | missense_variant | 2/4 | 1 | |||
HAS3 | ENST00000566118.5 | c.214C>T | p.Arg72Cys | missense_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00346 AC: 526AN: 152224Hom.: 5 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000915 AC: 228AN: 249128Hom.: 1 AF XY: 0.000638 AC XY: 86AN XY: 134880
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GnomAD4 exome AF: 0.000410 AC: 598AN: 1459840Hom.: 1 Cov.: 32 AF XY: 0.000368 AC XY: 267AN XY: 726320
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GnomAD4 genome ? AF: 0.00345 AC: 526AN: 152342Hom.: 5 Cov.: 33 AF XY: 0.00338 AC XY: 252AN XY: 74484
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ESP6500AA
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129
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3478
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D;.;T;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;P;.;P
Vest4
MVP
MPC
1.4
ClinPred
T
GERP RS
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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