rs201504622

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM2PM5BP4BS2

The NM_000127.3(EXT1):ā€‹c.1360G>Cā€‹(p.Val454Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V454I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

EXT1
NM_000127.3 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.03
Variant links:
Genes affected
EXT1 (HGNC:3512): (exostosin glycosyltransferase 1) This gene encodes an endoplasmic reticulum-resident type II transmembrane glycosyltransferase involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type I form of multiple exostoses. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr8-117822522-C-T is described in Lovd as [Likely_pathogenic].
BP4
Computational evidence support a benign effect (MetaRNN=0.33404368).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EXT1NM_000127.3 linkuse as main transcriptc.1360G>C p.Val454Leu missense_variant 5/11 ENST00000378204.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EXT1ENST00000378204.7 linkuse as main transcriptc.1360G>C p.Val454Leu missense_variant 5/111 NM_000127.3 P1
EXT1ENST00000684189.1 linkuse as main transcriptn.827G>C non_coding_transcript_exon_variant 5/11
EXT1ENST00000436216.2 linkuse as main transcriptc.*161G>C 3_prime_UTR_variant, NMD_transcript_variant 6/63
EXT1ENST00000437196.1 linkuse as main transcriptc.*251G>C 3_prime_UTR_variant, NMD_transcript_variant 4/105

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250834
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135584
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:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460996
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726838
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:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Uncertain
0.048
T
BayesDel_noAF
Uncertain
0.010
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T
Eigen
Benign
-0.21
Eigen_PC
Benign
0.064
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.051
D
MetaRNN
Benign
0.33
T
MetaSVM
Uncertain
0.091
D
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-0.78
N
REVEL
Uncertain
0.38
Sift
Benign
0.30
T
Sift4G
Benign
0.43
T
Polyphen
0.0030
B
Vest4
0.48
MutPred
0.32
Gain of sheet (P = 0.1945);
MVP
0.76
MPC
0.44
ClinPred
0.16
T
GERP RS
6.1
Varity_R
0.13
gMVP
0.73

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: rs201504622; hg19: chr8-118834761; API