11-124754319-G-A

Variant names:

• chr11-124754319-G-A
• NM_138961.3:c.752C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138961.3(ESAM):​c.752C>T​(p.Ala251Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ESAM NM_138961.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.369475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESAM	NM_138961.3	c.752C>T	p.Ala251Val	missense_variant	Exon 6 of 7	ENST00000278927.10	NP_620411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESAM	ENST00000278927.10	c.752C>T	p.Ala251Val	missense_variant	Exon 6 of 7	1	NM_138961.3	ENSP00000278927.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.752C>T (p.A251V) alteration is located in exon 6 (coding exon 6) of the ESAM gene. This alteration results from a C to T substitution at nucleotide position 752, causing the alanine (A) at amino acid position 251 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	0.0042	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.5	.;M;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.25	.;T;.
Polyphen		0.35, 0.76	.;B;P
Vest4		0.14
MutPred		0.66		.;Gain of sheet (P = 0.0028);.;
MVP		0.83
MPC		0.053
ClinPred		0.88	D
GERP RS		5.6
Varity_R		0.17
gMVP		0.62

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: chr11-124624215;