Variant chr1-26022696-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004455.3(EXTL1):c.50C>T(p.Ser17Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000889 in 1,612,788 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00093 ( 2 hom. )

Consequence

EXTL1
NM_004455.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.912

Variant links:

Genes affected

EXTL1 (HGNC:3515): (exostosin like glycosyltransferase 1) This gene is a member of the multiple exostoses (EXT) family of glycosyltransferases, which function in the chain polymerization of heparan sulfate and heparin. The encoded protein harbors alpha 1,4- N-acetylglucosaminyltransferase activity, and is involved in chain elongation of heparan sulfate and possibly heparin. [provided by RefSeq, Jul 2008]

EXTL1 links:

EXTL1 (HGNC:):

EXTL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04083234).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXTL1	NM_004455.3 linkuse as main transcript	c.50C>T	p.Ser17Phe	missense_variant	1/11	ENST00000374280.4	NP_004446.2	Q92935
EXTL1	XM_005245779.5 linkuse as main transcript	c.50C>T	p.Ser17Phe	missense_variant	1/10		XP_005245836.1
EXTL1	XM_017000650.3 linkuse as main transcript	c.50C>T	p.Ser17Phe	missense_variant	1/8		XP_016856139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXTL1	ENST00000374280.4 linkuse as main transcript	c.50C>T	p.Ser17Phe	missense_variant	1/11	1	NM_004455.3	ENSP00000363398.3		Q92935
EXTL1	ENST00000481377.5 linkuse as main transcript	n.61+2752C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000523

AC:

131

AN:

250290

Hom.:

AF XY:

0.000481

AC XY:

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000932

AC:

1362

AN:

1460662

Hom.:

Cov.:

AF XY:

0.000878

AC XY:

638

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000244

Gnomad4 NFE exome

AF:

0.00119

Gnomad4 OTH exome

AF:

0.000365

GnomAD4 genome

AF:

0.000473

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000845

Hom.:

Bravo

AF:

0.000382

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000642

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.50C>T (p.S17F) alteration is located in exon 1 (coding exon 1) of the EXTL1 gene. This alteration results from a C to T substitution at nucleotide position 50, causing the serine (S) at amino acid position 17 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0059

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.041

MetaSVM

Uncertain

-0.089

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.6

REVEL

Benign

0.23

Sift

Benign

0.48

Sift4G

Benign

0.33

Polyphen

0.030

Vest4

0.24

MVP

0.68

MPC

0.34

ClinPred

0.012

GERP RS

3.4

Varity_R

0.072

gMVP

0.67

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