3-50299230-T-C

Variant names:

• chr3-50299230-T-C
• rs2285044
• NM_003549.4:c.-35A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003549.4(HYAL3):​c.-35A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 1,614,042 control chromosomes in the GnomAD database, including 13,010 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 0.10 (2271 hom., cov: 33)
  • Exomes 𝑓: 0.037 (10739 hom.)
• Consequence: HYAL3 NM_003549.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 6 publications found

Genes affected

HYAL3 (HGNC:5322): (hyaluronidase 3) This gene encodes a member of the hyaluronidase family. Hyaluronidases are endoglycosidase enzymes that degrade hyaluronan, one of the major glycosaminoglycans of the extracellular matrix. The regulated turnover of hyaluronan plays a critical role in many biological processes including cell proliferation, migration and differentiation. The encoded protein may also play an important role in sperm function. This gene is one of several related genes in a region of chromosome 3p21.3 associated with tumor suppression, and the expression of specific transcript variants may be indicative of tumor status. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and some isoforms may lack hyaluronidase activity. This gene overlaps and is on the same strand as N-acetyltransferase 6 (GCN5-related), and some transcripts of each gene share a portion of the first exon. [provided by RefSeq, Jan 2011]

NAA80 (HGNC:30252): (N-alpha-acetyltransferase 80, NatH catalytic subunit) This gene encodes a member of the N-acetyltransferase family. N-acetyltransferases modify proteins by transferring acetyl groups from acetyl CoA to the N-termini of protein substrates. The encoded protein is a cytoplasmic N-acetyltransferase with a substrate specificity for proteins with an N-terminal methionine. This gene is located in the tumor suppressor gene region on chromosome 3p21.3 and the encoded protein may play a role in cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed. This gene overlaps and is on the same strand as hyaluronoglucosaminidase 3, and some transcripts of each gene share a portion of the first exon. [provided by RefSeq, Jan 2011]

ENSG00000295204 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYAL3	NM_003549.4	c.-35A>G		5_prime_UTR_variant	Exon 1 of 4	ENST00000336307.6	NP_003540.2
NAA80	NM_001200016.2	c.-227A>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000443094.3	NP_001186945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYAL3	ENST00000336307.6	c.-35A>G		5_prime_UTR_variant	Exon 1 of 4	1	NM_003549.4	ENSP00000337425.1
NAA80	ENST00000443094.3	c.-227A>G		5_prime_UTR_variant	Exon 1 of 2	1	NM_001200016.2	ENSP00000410610.2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15720 AN: 152144 Hom.: 2269 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00360

Gnomad OTH AF: 0.0866

GnomAD2 exomes AF: 0.122 AC: 29997 AN: 246542 AF XY: 0.0986

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.411

Gnomad ASJ exome AF: 0.00329

Gnomad EAS exome AF: 0.612

Gnomad FIN exome AF: 0.0445

Gnomad NFE exome AF: 0.00358

Gnomad OTH exome AF: 0.0675

GnomAD4 exome AF: 0.0368 AC: 53836 AN: 1461780 Hom.: 10739 Cov.: 31 AF XY: 0.0334 AC XY: 24262 AN XY: 727208

African (AFR) AF: 0.193 AC: 6475 AN: 33480

American (AMR) AF: 0.389 AC: 17392 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00421 AC: 110 AN: 26130

East Asian (EAS) AF: 0.535 AC: 21224 AN: 39690

South Asian (SAS) AF: 0.0102 AC: 881 AN: 86256

European-Finnish (FIN) AF: 0.0441 AC: 2351 AN: 53360

Middle Eastern (MID) AF: 0.00728 AC: 42 AN: 5766

European-Non Finnish (NFE) AF: 0.00174 AC: 1939 AN: 1111990

Other (OTH) AF: 0.0567 AC: 3422 AN: 60396

GnomAD4 genome AF: 0.103 AC: 15748 AN: 152262 Hom.: 2271 Cov.: 33 AF XY: 0.110 AC XY: 8184 AN XY: 74458

African (AFR) AF: 0.181 AC: 7533 AN: 41546

American (AMR) AF: 0.266 AC: 4076 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.600 AC: 3095 AN: 5158

South Asian (SAS) AF: 0.0209 AC: 101 AN: 4828

European-Finnish (FIN) AF: 0.0467 AC: 496 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00360 AC: 245 AN: 68022

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0483 Hom.: 656

Bravo AF: 0.129

Asia WGS AF: 0.205 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.6
DANN	Benign	0.68
PhyloP100		-1.1
PromoterAI		0.24	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs2285044; hg19: chr3-50336661; COSMIC: COSV56497154; COSMIC: COSV56497154;