15-88879056-G-T

Variant names:

• chr15-88879056-G-T
• NM_178232.4:c.707C>A

Variant summary

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

The NM_178232.4(HAPLN3):​c.707C>A​(p.Pro236Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HAPLN3 NM_178232.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

Genes affected

HAPLN3 (HGNC:21446): (hyaluronan and proteoglycan link protein 3) This gene belongs to the hyaluronan and proteoglycan binding link protein gene family. The protein encoded by this gene may function in hyaluronic acid binding and cell adhesion. [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=0.06642482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAPLN3	NM_178232.4	c.707C>A	p.Pro236Gln	missense_variant	Exon 4 of 5	ENST00000359595.8	NP_839946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAPLN3	ENST00000359595.8	c.707C>A	p.Pro236Gln	missense_variant	Exon 4 of 5	1	NM_178232.4	ENSP00000352606.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453708 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722632

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: 0.0000193

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	0.077
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.4
DANN	Benign	0.83
DEOGEN2	Benign	0.0068	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.20	N;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.71	N;N
REVEL	Benign	0.044
Sift	Benign	0.63	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0080	B;.
Vest4		0.27
MutPred		0.40		Gain of catalytic residue at P236 (P = 0.0172);.;
MVP		0.18
MPC		0.34
ClinPred		0.039	T
GERP RS		-0.12
Varity_R		0.023
gMVP		0.16

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: chr15-89422287;