rs770631310

Variant summary

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

The NM_007036.5(ESM1):​c.517G>T​(p.Gly173Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. G173R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ESM1
NM_007036.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.966
Variant links:
Genes affected
ESM1 (HGNC:3466): (endothelial cell specific molecule 1) This gene encodes a secreted protein which is mainly expressed in the endothelial cells in human lung and kidney tissues. The expression of this gene is regulated by cytokines, suggesting that it may play a role in endothelium-dependent pathological disorders. The transcript contains multiple polyadenylation and mRNA instability signals. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 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=0.073578).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ESM1NM_007036.5 linkc.517G>T p.Gly173Trp missense_variant Exon 3 of 3 ENST00000381405.5 NP_008967.1 Q9NQ30-1
ESM1NM_001135604.2 linkc.367G>T p.Gly123Trp missense_variant Exon 2 of 2 NP_001129076.1 Q9NQ30-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ESM1ENST00000381405.5 linkc.517G>T p.Gly173Trp missense_variant Exon 3 of 3 1 NM_007036.5 ENSP00000370812.4 Q9NQ30-1
ESM1ENST00000381403.4 linkc.367G>T p.Gly123Trp missense_variant Exon 2 of 2 1 ENSP00000370810.4 Q9NQ30-2
ESM1ENST00000598310.5 linkn.295G>T non_coding_transcript_exon_variant Exon 3 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251358
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135870
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:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461582
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
727112
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:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
12
DANN
Benign
0.55
DEOGEN2
Benign
0.018
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.089
N
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.074
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.46
N;N
REVEL
Benign
0.18
Sift
Uncertain
0.019
D;D
Sift4G
Uncertain
0.024
D;D
Polyphen
0.98
D;.
Vest4
0.21
MutPred
0.29
Loss of disorder (P = 0.0094);.;
MVP
0.076
MPC
1.5
ClinPred
0.20
T
GERP RS
1.6
Varity_R
0.075
gMVP
0.47

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: rs770631310; hg19: chr5-54275198; API