5-83644586-C-G

Position:

• chr5-83644586-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001884.4(HAPLN1):​c.552G>C​(p.Gln184His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,178 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: HAPLN1 NM_001884.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

Genes affected

HAPLN1 (HGNC:2380): (hyaluronan and proteoglycan link protein 1) Predicted to enable hyaluronic acid binding activity. Predicted to be an extracellular matrix structural constituent conferring compression resistance. Predicted to be involved in central nervous system development and skeletal system development. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAPLN1	NM_001884.4	c.552G>C	p.Gln184His	missense_variant	4/5	ENST00000274341.9	NP_001875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAPLN1	ENST00000274341.9	c.552G>C	p.Gln184His	missense_variant	4/5	1	NM_001884.4	ENSP00000274341.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426178 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 706740

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.552G>C (p.Q184H) alteration is located in exon 4 (coding exon 3) of the HAPLN1 gene. This alteration results from a G to C substitution at nucleotide position 552, causing the glutamine (Q) at amino acid position 184 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.013	D;.;D
Polyphen		1.0	D;.;.
Vest4		0.76
MutPred		0.56		Gain of catalytic residue at D185 (P = 0.1333);Gain of catalytic residue at D185 (P = 0.1333);Gain of catalytic residue at D185 (P = 0.1333);
MVP		0.70
MPC		0.65
ClinPred		0.99	D
GERP RS		2.1
Varity_R		0.83
gMVP		0.78

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: chr5-82940405;