dbSNP rs770631310: ESM1:p.Gly173Trp (chr5-54979370-C-A) – ACMG Classification: Uncertain_significance (0 pts)

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

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]

ESM1 links:

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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=0.073578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESM1	NM_007036.5 link	c.517G>T	p.Gly173Trp	missense_variant	Exon 3 of 3	ENST00000381405.5	NP_008967.1	Q9NQ30-1
ESM1	NM_001135604.2 link	c.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	UniProt
ESM1	ENST00000381405.5 link	c.517G>T	p.Gly173Trp	missense_variant	Exon 3 of 3	1	NM_007036.5	ENSP00000370812.4	Q9NQ30-1
ESM1	ENST00000381403.4 link	c.367G>T	p.Gly123Trp	missense_variant	Exon 2 of 2	1		ENSP00000370810.4	Q9NQ30-2
ESM1	ENST00000598310.5 link	n.295G>T		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251358

Hom.:

AF XY:

0.0000294

AC XY:

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:

AN:

1461582

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

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.:

ExAC

AF:

0.00000824

AC:

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

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.55

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.22

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over