Genetic Variant EXTL1:p.Thr186Met (chr1-26023203-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004455.3(EXTL1):c.557C>T(p.Thr186Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

EXTL1
NM_004455.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.132

Publications

1 publications found

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:

ENSG00000310101 (HGNC:):

ENSG00000310101 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38498068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004455.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXTL1	NM_004455.3	MANE Select	c.557C>T	p.Thr186Met	missense	Exon 1 of 11	NP_004446.2	Q92935

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXTL1	ENST00000374280.4	TSL:1 MANE Select	c.557C>T	p.Thr186Met	missense	Exon 1 of 11	ENSP00000363398.3	Q92935
EXTL1	ENST00000882621.1		c.557C>T	p.Thr186Met	missense	Exon 1 of 11	ENSP00000552680.1
EXTL1	ENST00000882616.1		c.557C>T	p.Thr186Met	missense	Exon 1 of 10	ENSP00000552675.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000240

AC:

AN:

249878

AF XY:

0.0000370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460270

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111046

Other (OTH)

AF:

0.0000166

AC:

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.38

MetaSVM

Uncertain

0.44

MutationAssessor

Uncertain

2.4

PhyloP100

-0.13

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.37

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

0.99

Vest4

0.057

MutPred

0.53

Loss of glycosylation at T186 (P = 0.0226)

MVP

0.65

MPC

0.35

ClinPred

0.27

GERP RS

1.3

Varity_R

0.073

gMVP

0.47

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over