rs6558073

Variant names:

• chr8-28756010-G-A
• rs6558073
• ENST00000696188.1:n.5859G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-28756010-G-A
• chr8-28756010-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000696188.1(EXTL3):​n.5859G>A variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EXTL3 ENST00000696188.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXTL3	NM_001437797.1	c.*5144G>A		3_prime_UTR_variant	Exon 6 of 6		NP_001424726.1
EXTL3	NM_001438399.1	c.*5144G>A		3_prime_UTR_variant	Exon 7 of 7		NP_001425328.1
EXTL3	NM_001438400.1	c.*5144G>A		3_prime_UTR_variant	Exon 8 of 8		NP_001425329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXTL3	ENST00000696188.1	n.5859G>A		non_coding_transcript_exon_variant	Exon 5 of 5
EXTL3	ENST00000696177.1	c.*5144G>A		3_prime_UTR_variant	Exon 6 of 6			ENSP00000512467.1
EXTL3	ENST00000696178.1	c.*5144G>A		3_prime_UTR_variant	Exon 7 of 7			ENSP00000512468.1
EXTL3	ENST00000696182.1	c.*5144G>A		3_prime_UTR_variant	Exon 5 of 5			ENSP00000512472.1

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.89
PhyloP100		-0.74

Splicing

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

Other links and lift over

dbSNP: rs6558073; hg19: chr8-28613527;