16-69109536-G-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001199280.2(HAS3):c.141G>T(p.Leu47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,236 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 (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Consequence
HAS3
NM_001199280.2 synonymous
NM_001199280.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.500
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP7
Synonymous conserved (PhyloP=0.5 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| HAS3 | NM_001199280.2 | c.141G>T | p.Leu47= | synonymous_variant | 2/4 | ENST00000569188.6 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HAS3 | ENST00000569188.6 | c.141G>T | p.Leu47= | synonymous_variant | 2/4 | 2 | NM_001199280.2 | P1 | |
| HAS3 | ENST00000306560.1 | c.141G>T | p.Leu47= | synonymous_variant | 2/4 | 1 | P1 | ||
| HAS3 | ENST00000219322.7 | c.141G>T | p.Leu47= | synonymous_variant | 2/4 | 1 | |||
| HAS3 | ENST00000566118.5 | c.141G>T | p.Leu47= | synonymous_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33
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GnomAD4 exome Cov.: 31
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GnomAD4 genome 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74376
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, no assertion criteria provided | literature only | Richard Lifton Laboratory, Yale University School of Medicine | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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