chr16-69109674-A-G

Variant names:

• chr16-69109674-A-G
• rs2232228
• NM_001199280.2:c.279A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001199280.2(HAS3):​c.279A>G​(p.Ala93Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,609,280 control chromosomes in the GnomAD database, including 137,883 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (10172 hom., cov: 33)
  • Exomes 𝑓: 0.41 (127711 hom.)
• Consequence: HAS3 NM_001199280.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 53 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=0.222 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAS3	NM_001199280.2	c.279A>G	p.Ala93Ala	synonymous_variant	Exon 2 of 4	ENST00000569188.6	NP_001186209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAS3	ENST00000569188.6	c.279A>G	p.Ala93Ala	synonymous_variant	Exon 2 of 4	2	NM_001199280.2	ENSP00000454731.1
HAS3	ENST00000306560.1	c.279A>G	p.Ala93Ala	synonymous_variant	Exon 2 of 4	1		ENSP00000304440.1
HAS3	ENST00000219322.7	c.279A>G	p.Ala93Ala	synonymous_variant	Exon 2 of 4	1		ENSP00000219322.3
HAS3	ENST00000566118.5	c.279A>G	p.Ala93Ala	synonymous_variant	Exon 2 of 4	5		ENSP00000456246.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51542 AN: 152016 Hom.: 10165 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.366

GnomAD2 exomes AF: 0.401 AC: 99027 AN: 246844 AF XY: 0.404

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.489

Gnomad EAS exome AF: 0.484

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.415 AC: 604230 AN: 1457146 Hom.: 127711 Cov.: 53 AF XY: 0.414 AC XY: 300305 AN XY: 725054

African (AFR) AF: 0.106 AC: 3559 AN: 33472

American (AMR) AF: 0.418 AC: 18657 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 12626 AN: 26104

East Asian (EAS) AF: 0.470 AC: 18640 AN: 39690

South Asian (SAS) AF: 0.364 AC: 31358 AN: 86220

European-Finnish (FIN) AF: 0.373 AC: 18328 AN: 49170

Middle Eastern (MID) AF: 0.316 AC: 1824 AN: 5766

European-Non Finnish (NFE) AF: 0.427 AC: 474641 AN: 1111696

Other (OTH) AF: 0.408 AC: 24597 AN: 60344

GnomAD4 genome AF: 0.339 AC: 51551 AN: 152134 Hom.: 10172 Cov.: 33 AF XY: 0.339 AC XY: 25209 AN XY: 74368

African (AFR) AF: 0.123 AC: 5099 AN: 41540

American (AMR) AF: 0.399 AC: 6109 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1674 AN: 3470

East Asian (EAS) AF: 0.492 AC: 2539 AN: 5158

South Asian (SAS) AF: 0.383 AC: 1845 AN: 4822

European-Finnish (FIN) AF: 0.369 AC: 3910 AN: 10584

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29176 AN: 67956

Other (OTH) AF: 0.362 AC: 763 AN: 2108

Alfa AF: 0.414 Hom.: 43888

Bravo AF: 0.332

Asia WGS AF: 0.413 AC: 1437 AN: 3478

EpiCase AF: 0.438

EpiControl AF: 0.438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.3
DANN	Benign	0.57
PhyloP100		0.22
Mutation Taster		=84/16	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2232228; hg19: chr16-69143577; COSMIC: COSV54707058; COSMIC: COSV54707058;