1-26023203-C-G

Variant summary

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

The NM_004455.3(EXTL1):​c.557C>G​(p.Thr186Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T186M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

EXTL1
NM_004455.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.132
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]

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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=0.1313217).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EXTL1NM_004455.3 linkc.557C>G p.Thr186Arg missense_variant Exon 1 of 11 ENST00000374280.4 NP_004446.2 Q92935
EXTL1XM_005245779.5 linkc.557C>G p.Thr186Arg missense_variant Exon 1 of 10 XP_005245836.1
EXTL1XM_017000650.3 linkc.557C>G p.Thr186Arg missense_variant Exon 1 of 8 XP_016856139.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EXTL1ENST00000374280.4 linkc.557C>G p.Thr186Arg missense_variant Exon 1 of 11 1 NM_004455.3 ENSP00000363398.3 Q92935
EXTL1ENST00000484339.1 linkn.15C>G non_coding_transcript_exon_variant Exon 1 of 4 3
EXTL1ENST00000481377.5 linkn.61+3259C>G intron_variant Intron 1 of 5 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
249878
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135306
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000887
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.0048
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
8.6
DANN
Benign
0.96
DEOGEN2
Benign
0.42
T
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.049
N
LIST_S2
Benign
0.44
T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.13
T
MetaSVM
Uncertain
0.11
D
MutationAssessor
Benign
1.3
L
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.23
Sift
Benign
0.055
T
Sift4G
Uncertain
0.019
D
Polyphen
0.030
B
Vest4
0.10
MutPred
0.57
Loss of glycosylation at T186 (P = 0.0226);
MVP
0.50
MPC
0.29
ClinPred
0.069
T
GERP RS
1.3
Varity_R
0.11
gMVP
0.55

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.

Other links and lift over

dbSNP: rs760157945; hg19: chr1-26349694; API