Genetic Variant NM_007036.5:c.445C>G (chr5-54982003-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007036.5(ESM1):c.445C>G(p.Leu149Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ESM1
NM_007036.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07549551).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007036.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESM1	NM_007036.5	MANE Select	c.445C>G	p.Leu149Val	missense	Exon 2 of 3	NP_008967.1	Q9NQ30-1
	ESM1	NM_001135604.2		c.302-2568C>G		intron	N/A	NP_001129076.1	Q9NQ30-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESM1	ENST00000381405.5	TSL:1 MANE Select	c.445C>G	p.Leu149Val	missense	Exon 2 of 3	ENSP00000370812.4	Q9NQ30-1
ESM1	ENST00000381403.4	TSL:1	c.302-2568C>G		intron	N/A	ENSP00000370810.4	Q9NQ30-2
ESM1	ENST00000598310.5	TSL:5	n.230-2568C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251304

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111890

Other (OTH)

AF:

0.0000166

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.013

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.68

M_CAP

Benign

0.0049

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

4.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.12

REVEL

Benign

0.029

Sift

Benign

0.22

Sift4G

Benign

0.41

Polyphen

0.057

Vest4

0.070

MutPred

0.16

Gain of disorder (P = 0.1586)

MVP

0.092

MPC

0.73

ClinPred

0.12

GERP RS

4.1

Varity_R

0.065

gMVP

0.45

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over