EXTL3 p.Arg339Arg

Variant names:

• chr8-28717073-G-G
• ENST00000220562.9:c.

Your query was ambiguous. Multiple possible variants found:

• chr8-28717074--
• chr8-28717076-G-T
• chr8-28717076-G-C
• chr8-28717076-G-A
• chr8-28717074-C-A
• chr8-28717074-CGG-AGA

Variant summary

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

The NM_001440.4(EXTL3):​c. variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EXTL3 NM_001440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78
• Publications: 0 publications found

Genes affected

EXTL3 (HGNC:3518): (exostosin like glycosyltransferase 3) This gene encodes a single-pass membrane protein which functions as a glycosyltransferase. The encoded protein catalyzes the transfer of N-acetylglucosamine to glycosaminoglycan chains. This reaction is important in heparin and heparan sulfate synthesis. Alternative splicing results in the multiple transcript variants. [provided by RefSeq, Nov 2012]

EXTL3 Gene-Disease associations (from GenCC):

• immunoskeletal dysplasia with neurodevelopmental abnormalities

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440.4. 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
	EXTL3	NM_001440.4	MANE Select	c.		intron	N/A	NP_001431.1	A0A384NPY9
	EXTL3	NM_001437797.1		c.		intron	N/A	NP_001424726.1	A0A384NPY9
	EXTL3	NM_001438399.1		c.		intron	N/A	NP_001425328.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXTL3	ENST00000220562.9	TSL:1 MANE Select	c.		exon_region	Exon 3 of 7	ENSP00000220562.4	O43909
	EXTL3	ENST00000696177.1		c.		exon_region	Exon 2 of 6	ENSP00000512467.1	O43909
	EXTL3	ENST00000696178.1		c.		exon_region	Exon 3 of 7	ENSP00000512468.1	O43909

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-28574590;