chr8-28756010-G-C

Position:

• chr8-28756010-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696177.1(EXTL3):​c.*5144G>C variant causes a 3 prime UTR 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 ENST00000696177.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
		n.28756010G>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXTL3	ENST00000696177.1	c.*5144G>C		3_prime_UTR_variant	6/6			ENSP00000512467.1
EXTL3	ENST00000696178.1	c.*5144G>C		3_prime_UTR_variant	7/7			ENSP00000512468.1
EXTL3	ENST00000696182.1	c.*5144G>C		3_prime_UTR_variant	5/5			ENSP00000512472.1
EXTL3	ENST00000696188.1	n.5859G>C		non_coding_transcript_exon_variant	5/5

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

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.459

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6558073; hg19: chr8-28613527;