5-54985468-A-T

Position:

• chr5-54985468-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007036.5(ESM1):​c.50T>A​(p.Val17Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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)
• Consequence: ESM1 NM_007036.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056096405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESM1	NM_007036.5	c.50T>A	p.Val17Glu	missense_variant	1/3	ENST00000381405.5
ESM1	NM_001135604.2	c.50T>A	p.Val17Glu	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESM1	ENST00000381405.5	c.50T>A	p.Val17Glu	missense_variant	1/3	1	NM_007036.5	P1
ESM1	ENST00000381403.4	c.50T>A	p.Val17Glu	missense_variant	1/2	1
ESM1	ENST00000601836.1	c.50T>A	p.Val17Glu	missense_variant	2/2	5
ESM1	ENST00000598310.5	n.230-6033T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.66
DEOGEN2	Benign	0.043	T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.17	N;N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.010	N;N;.
REVEL	Benign	0.0050
Sift	Benign	0.050	D;T;.
Sift4G	Benign	0.097	T;T;.
Polyphen		0.20	B;.;.
Vest4		0.19
MutPred		0.35		Loss of catalytic residue at S21 (P = 0.1546);Loss of catalytic residue at S21 (P = 0.1546);Loss of catalytic residue at S21 (P = 0.1546);
MVP		0.12
MPC		1.1
ClinPred		0.28	T
GERP RS		-0.26
Varity_R		0.13
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-54281296;