rs760157945

Variant summary

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

The NM_004455.3(EXTL1):​c.557C>A​(p.Thr186Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

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]

Genome browser will be placed here

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=0.11371204).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EXTL1NM_004455.3 linkc.557C>A p.Thr186Lys missense_variant Exon 1 of 11 ENST00000374280.4 NP_004446.2 Q92935
EXTL1XM_005245779.5 linkc.557C>A p.Thr186Lys missense_variant Exon 1 of 10 XP_005245836.1
EXTL1XM_017000650.3 linkc.557C>A p.Thr186Lys 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>A p.Thr186Lys missense_variant Exon 1 of 11 1 NM_004455.3 ENSP00000363398.3 Q92935
EXTL1ENST00000484339.1 linkn.15C>A non_coding_transcript_exon_variant Exon 1 of 4 3
EXTL1ENST00000481377.5 linkn.61+3259C>A intron_variant Intron 1 of 5 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460268
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
726234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Uncertain
0.039
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
9.5
DANN
Benign
0.87
DEOGEN2
Benign
0.37
T
Eigen
Benign
-0.98
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.40
T
M_CAP
Uncertain
0.095
D
MetaRNN
Benign
0.11
T
MetaSVM
Uncertain
-0.072
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.25
Sift
Benign
0.062
T
Sift4G
Benign
0.16
T
Polyphen
0.054
B
Vest4
0.090
MutPred
0.58
Gain of ubiquitination at T186 (P = 0.0192);
MVP
0.37
MPC
0.29
ClinPred
0.15
T
GERP RS
1.3
Varity_R
0.076
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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