rs1180407813

Variant names:

• chr19-19257870-C-A
• NM_023002.3:c.1156G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-19257870-C-A
• chr19-19257870-C-G
• chr19-19257870-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023002.3(HAPLN4):​c.1156G>T​(p.Gly386Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000782 in 1,279,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G386S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: HAPLN4 NM_023002.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520

Genes affected

HAPLN4 (HGNC:31357): (hyaluronan and proteoglycan link protein 4) Predicted to enable hyaluronic acid binding activity. Predicted to be involved in central nervous system development and skeletal system development. Predicted to be located in extracellular region. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267629 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20781413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAPLN4	NM_023002.3	c.1156G>T	p.Gly386Cys	missense_variant	Exon 5 of 5	ENST00000291481.8	NP_075378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAPLN4	ENST00000291481.8	c.1156G>T	p.Gly386Cys	missense_variant	Exon 5 of 5	1	NM_023002.3	ENSP00000291481.5
ENSG00000267629	ENST00000586064.3	n.2287G>T		non_coding_transcript_exon_variant	Exon 12 of 12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.82e-7 AC: 1 AN: 1279156 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 628122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000578

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.092
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.37
MutPred		0.41		Loss of disorder (P = 0.0109);
MVP		0.66
MPC		0.74
ClinPred		0.61	D
GERP RS		3.5
Varity_R		0.38
gMVP		0.79

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: chr19-19368679;