Genetic Variant ESAM:p.Thr10Ile (chr11-124762126-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_138961.3(ESAM):c.29C>T(p.Thr10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,457,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ESAM
NM_138961.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.341

Variant links:

Genes affected

ESAM (HGNC:17474): (endothelial cell adhesion molecule) Enables cell-cell adhesion mediator activity. Involved in several processes, including bicellular tight junction assembly; cell-cell adhesion; and regulation of actin cytoskeleton organization. Located in cell-cell junction and plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ESAM links:

ESAM-AS1 (HGNC:55558): (ESAM antisense RNA 1)

ESAM-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26666525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESAM	NM_138961.3 link	c.29C>T	p.Thr10Ile	missense_variant	Exon 1 of 7	ENST00000278927.10	NP_620411.2	Q96AP7-1
ESAM-AS1	NR_120577.1 link	n.281-2603G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESAM	ENST00000278927.10 link	c.29C>T	p.Thr10Ile	missense_variant	Exon 1 of 7	1	NM_138961.3	ENSP00000278927.5		Q96AP7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1457324

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

725040

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.29C>T (p.T10I) alteration is located in exon 1 (coding exon 1) of the ESAM gene. This alteration results from a C to T substitution at nucleotide position 29, causing the threonine (T) at amino acid position 10 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.10

.;T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.48

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.4

M;M;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.099

Sift

Pathogenic

0.0

D;D;T

Sift4G

Uncertain

0.025

.;D;.

Polyphen

0.0050

.;B;.

Vest4

0.093

MutPred

0.64

Loss of catalytic residue at T10 (P = 0.0348);Loss of catalytic residue at T10 (P = 0.0348);Loss of catalytic residue at T10 (P = 0.0348);

MVP

0.71

MPC

0.047

ClinPred

0.56

GERP RS

1.5

Varity_R

0.052

gMVP

0.51

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over