Variant 1-26023148-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004455.3(EXTL1):c.502C>T(p.Pro168Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,608 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 1 hom. )

Consequence

EXTL1
NM_004455.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.985

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0987643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXTL1	NM_004455.3 linkuse as main transcript	c.502C>T	p.Pro168Ser	missense_variant	1/11	ENST00000374280.4	NP_004446.2	Q92935
EXTL1	XM_005245779.5 linkuse as main transcript	c.502C>T	p.Pro168Ser	missense_variant	1/10		XP_005245836.1
EXTL1	XM_017000650.3 linkuse as main transcript	c.502C>T	p.Pro168Ser	missense_variant	1/8		XP_016856139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EXTL1	ENST00000374280.4 linkuse as main transcript	c.502C>T	p.Pro168Ser	missense_variant	1/11	1	NM_004455.3	ENSP00000363398.3	Q92935
EXTL1	ENST00000481377.5 linkuse as main transcript	n.61+3204C>T		intron_variant		3
EXTL1	ENST00000484339.1 linkuse as main transcript	n.-41C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250976

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Aug 06, 2024

The c.502C>T (p.P168S) 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 502, causing the proline (P) at amino acid position 168 to be replaced by a serine (S). 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

0.066

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.27

CADD

Benign

1.8

DANN

Benign

0.71

DEOGEN2

Benign

0.18

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.099

MetaSVM

Uncertain

-0.051

MutationAssessor

Benign

0.53

PrimateAI

Benign

0.28

PROVEAN

Benign

1.3

REVEL

Benign

0.25

Sift

Benign

0.25

Sift4G

Benign

0.44

Polyphen

0.0010

Vest4

0.056

MutPred

0.65

Loss of catalytic residue at P168 (P = 0.016);

MVP

0.60

MPC

0.24

ClinPred

0.062

GERP RS

2.3

Varity_R

0.031

gMVP

0.39

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