rs782812423

Variant names:

• chr3-50300526-G-A
• NM_033159.4:c.1265C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-50300526-G-A
• chr3-50300526-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033159.4(HYAL1):​c.1265C>T​(p.Pro422Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P422R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: HYAL1 NM_033159.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65

Genes affected

HYAL1 (HGNC:5320): (hyaluronidase 1) This gene encodes a lysosomal hyaluronidase. Hyaluronidases intracellularly degrade hyaluronan, one of the major glycosaminoglycans of the extracellular matrix. Hyaluronan is thought to be involved in cell proliferation, migration and differentiation. This enzyme is active at an acidic pH and is the major hyaluronidase in plasma. Mutations in this gene are associated with mucopolysaccharidosis type IX, or hyaluronidase deficiency. The gene is one of several related genes in a region of chromosome 3p21.3 associated with tumor suppression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06566286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYAL1	NM_033159.4	c.1265C>T	p.Pro422Leu	missense_variant	Exon 4 of 4	ENST00000395144.7	NP_149349.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYAL1	ENST00000395144.7	c.1265C>T	p.Pro422Leu	missense_variant	Exon 4 of 4	1	NM_033159.4	ENSP00000378576.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.29
DANN	Benign	0.87
DEOGEN2	Benign	0.30	T;T;T;T;.;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.84	.;.;T;.;T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.066	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;L;L;.;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.7	N;N;.;N;N;N;D
REVEL	Benign	0.069
Sift	Benign	0.43	T;T;.;T;T;T;T
Sift4G	Benign	0.33	T;T;T;T;T;T;T
Polyphen		0.35	B;B;B;B;B;.;.
Vest4		0.15
MutPred		0.41		Gain of catalytic residue at P422 (P = 0.0021);Gain of catalytic residue at P422 (P = 0.0021);Gain of catalytic residue at P422 (P = 0.0021);Gain of catalytic residue at P422 (P = 0.0021);.;.;.;
MVP		0.10
MPC		0.22
ClinPred		0.43	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.099
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-50337957;