NM_001440.4:c.1015_1017delCGGinsAGA

Variant names:

• chr8-28717074-CGG-AGA
• NM_001440.4:c.1015_1017delCGGinsAGA
• EXTL3 p.340

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001440.4(EXTL3):​c.1015_1017delCGGinsAGA​(p.340) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R339R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EXTL3 NM_001440.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.78
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.1015_1017delCGGinsAGA	p.340	synonymous	N/A	NP_001431.1	A0A384NPY9
	EXTL3	NM_001437797.1		c.1015_1017delCGGinsAGA	p.340	synonymous	N/A	NP_001424726.1	A0A384NPY9
	EXTL3	NM_001438399.1		c.1015_1017delCGGinsAGA	p.340	synonymous	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.1015_1017delCGGinsAGA	p.340	synonymous	N/A	ENSP00000220562.4	O43909
	EXTL3	ENST00000696177.1		c.1015_1017delCGGinsAGA	p.340	synonymous	N/A	ENSP00000512467.1	O43909
	EXTL3	ENST00000696178.1		c.1015_1017delCGGinsAGA	p.340	synonymous	N/A	ENSP00000512468.1	O43909

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.8

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: chr8-28574591;