8-28621375-A-G

Variant names:

• chr8-28621375-A-G
• rs352428
• ENST00000522725.5:n.314+13617A>G

Variant summary

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

The ENST00000522725.5(EXTL3):​n.314+13617A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,202 control chromosomes in the GnomAD database, including 61,908 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 0.90 (61908 hom., cov: 31)
• Consequence: EXTL3 ENST00000522725.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 10 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522725.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXTL3	ENST00000522725.5	TSL:4	n.314+13617A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136835 AN: 152084 Hom.: 61854 Cov.: 31

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.900 AC: 136940 AN: 152202 Hom.: 61908 Cov.: 31 AF XY: 0.896 AC XY: 66627 AN XY: 74392

African (AFR) AF: 0.978 AC: 40636 AN: 41566

American (AMR) AF: 0.895 AC: 13674 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2869 AN: 3470

East Asian (EAS) AF: 0.879 AC: 4551 AN: 5180

South Asian (SAS) AF: 0.816 AC: 3937 AN: 4824

European-Finnish (FIN) AF: 0.845 AC: 8917 AN: 10552

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59390 AN: 68016

Other (OTH) AF: 0.872 AC: 1844 AN: 2114

Alfa AF: 0.881 Hom.: 205071

Bravo AF: 0.911

Asia WGS AF: 0.837 AC: 2911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		-0.74

Splicing

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

Other links and lift over

dbSNP: rs352428; hg19: chr8-28478892;