16-69115194-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001199280.2(HAS3):c.1590A>G(p.Leu530=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,567,160 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (159 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (144 hom.)
• Consequence: HAS3 NM_001199280.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.92

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-69115194-A-G is Benign according to our data. Variant chr16-69115194-A-G is described in ClinVar as [Benign]. Clinvar id is 781209.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAS3	NM_001199280.2	c.1590A>G	p.Leu530=	synonymous_variant	4/4	ENST00000569188.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAS3	ENST00000569188.6	c.1590A>G	p.Leu530=	synonymous_variant	4/4	2	NM_001199280.2	P1
HAS3	ENST00000306560.1	c.1590A>G	p.Leu530=	synonymous_variant	4/4	1		P1
HAS3	ENST00000219322.7	c.738+1652A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3888 AN: 151946 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00783 AC: 1663 AN: 212490 Hom.: 59 AF XY: 0.00567 AC XY: 642 AN XY: 113310

Gnomad AFR exome AF: 0.0909

Gnomad AMR exome AF: 0.00574

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000564

Gnomad SAS exome AF: 0.0000921

Gnomad FIN exome AF: 0.0000529

Gnomad NFE exome AF: 0.000366

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00284 AC: 4020 AN: 1415096 Hom.: 144 Cov.: 34 AF XY: 0.00246 AC XY: 1721 AN XY: 699078

Gnomad4 AFR exome AF: 0.0929

Gnomad4 AMR exome AF: 0.00638

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000509

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.0000584

Gnomad4 NFE exome AF: 0.000348

Gnomad4 OTH exome AF: 0.00644

GnomAD4 genome AF: 0.0256 AC: 3893 AN: 152064 Hom.: 159 Cov.: 32 AF XY: 0.0253 AC XY: 1880 AN XY: 74310

Gnomad4 AFR AF: 0.0876

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0142 Hom.: 44

Bravo AF: 0.0295

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.3
Dann	Benign	0.59

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

Other links and lift over

dbSNP: rs2232232; hg19: chr16-69149097;