ENST00000696188.1:n.5859G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696188.1(EXTL3):​n.5859G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,046 control chromosomes in the GnomAD database, including 15,397 homozygotes. 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: 𝑓 0.45 (15397 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXTL3	NM_001437797.1	c.*5144G>C		3_prime_UTR_variant	Exon 6 of 6		NP_001424726.1
EXTL3	NM_001438399.1	c.*5144G>C		3_prime_UTR_variant	Exon 7 of 7		NP_001425328.1
EXTL3	NM_001438400.1	c.*5144G>C		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>C		non_coding_transcript_exon_variant	Exon 5 of 5
EXTL3	ENST00000696177.1	c.*5144G>C		3_prime_UTR_variant	Exon 6 of 6			ENSP00000512467.1
EXTL3	ENST00000696178.1	c.*5144G>C		3_prime_UTR_variant	Exon 7 of 7			ENSP00000512468.1
EXTL3	ENST00000696182.1	c.*5144G>C		3_prime_UTR_variant	Exon 5 of 5			ENSP00000512472.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68284 AN: 151928 Hom.: 15379 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.449 AC: 68326 AN: 152046 Hom.: 15397 Cov.: 32 AF XY: 0.450 AC XY: 33470 AN XY: 74318

African (AFR) AF: 0.416 AC: 17268 AN: 41472

American (AMR) AF: 0.392 AC: 5985 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3470

East Asian (EAS) AF: 0.436 AC: 2255 AN: 5176

South Asian (SAS) AF: 0.417 AC: 2009 AN: 4814

European-Finnish (FIN) AF: 0.542 AC: 5715 AN: 10552

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32224 AN: 67970

Other (OTH) AF: 0.459 AC: 964 AN: 2102

Alfa AF: 0.453 Hom.: 1934

Bravo AF: 0.437

Asia WGS AF: 0.408 AC: 1423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.22
DANN	Benign	0.40
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;