rs116659770

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001440.4(EXTL3):c.1324G>C(p.Val442Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,614,190 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 43 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 42 hom. )

Consequence

EXTL3
NM_001440.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.62

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037114024).

BP6

Variant 8-28717383-G-C is Benign according to our data. Variant chr8-28717383-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 446049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1889/152302) while in subpopulation AFR AF= 0.0424 (1761/41554). AF 95% confidence interval is 0.0407. There are 43 homozygotes in gnomad4. There are 868 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXTL3	NM_001440.4 link	c.1324G>C	p.Val442Leu	missense_variant	Exon 3 of 7	ENST00000220562.9	NP_001431.1	O43909A0A384NPY9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXTL3	ENST00000220562.9 link	c.1324G>C	p.Val442Leu	missense_variant	Exon 3 of 7	1	NM_001440.4	ENSP00000220562.4		O43909

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1887

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00336

AC:

844

AN:

251448

Hom.:

AF XY:

0.00230

AC XY:

312

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0434

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00142

AC:

2073

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

881

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0460

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.00371

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000123

Gnomad4 OTH exome

AF:

0.00296

GnomAD4 genome

AF:

0.0124

AC:

1889

AN:

152302

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

868

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0424

Gnomad4 AMR

AF:

0.00556

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00229

Hom.:

Bravo

AF:

0.0143

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0411

AC:

181

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00404

AC:

491

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 27, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Immunoskeletal dysplasia with neurodevelopmental abnormalities

Benign:1

May 18, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.27

CADD

Benign

7.0

DANN

Benign

0.67

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

D;D

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.74

.;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.66

N;N

REVEL

Benign

0.25

Sift

Benign

0.51

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.0040

.;B

Vest4

0.14

MVP

0.69

MPC

0.31

ClinPred

0.0036

GERP RS

-0.76

Varity_R

0.042

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over