15-88878004-C-A

Variant names:

• chr15-88878004-C-A
• rs760853689
• NM_178232.4:c.1049G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178232.4(HAPLN3):​c.1049G>T​(p.Arg350Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. R350H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HAPLN3 NM_178232.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10173756).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178232.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAPLN3	NM_178232.4	MANE Select	c.1049G>T	p.Arg350Leu	missense	Exon 5 of 5	NP_839946.1	Q96S86
	HAPLN3	NM_001307952.2		c.1235G>T	p.Arg412Leu	missense	Exon 6 of 6	NP_001294881.1	H3BTH8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAPLN3	ENST00000359595.8	TSL:1 MANE Select	c.1049G>T	p.Arg350Leu	missense	Exon 5 of 5	ENSP00000352606.4	Q96S86
	HAPLN3	ENST00000562889.5	TSL:5	c.1235G>T	p.Arg412Leu	missense	Exon 6 of 6	ENSP00000457180.1	H3BTH8
	HAPLN3	ENST00000969266.1		c.1091G>T	p.Arg364Leu	missense	Exon 6 of 6	ENSP00000639325.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.7
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.18
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.059
Sift	Benign	0.15	T
Sift4G	Benign	0.19	T
Polyphen		0.48	P
Vest4		0.16
MutPred		0.51		Loss of disorder (P = 0.0116)
MVP		0.24
MPC		0.26
ClinPred		0.30	T
GERP RS		0.39
Varity_R		0.072
gMVP		0.45
Mutation Taster		=86/14	polymorphism

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: rs760853689; hg19: chr15-89421235;