11-124762120-A-T

Variant names:

• chr11-124762120-A-T
• NM_138961.3:c.35T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_138961.3(ESAM):​c.35T>A​(p.Leu12*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ESAM NM_138961.3 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 0.674

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

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.97 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-124762120-A-T is Pathogenic according to our data. Variant chr11-124762120-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1810272.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-124762120-A-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESAM	NM_138961.3	c.35T>A	p.Leu12*	stop_gained	Exon 1 of 7	ENST00000278927.10	NP_620411.2
ESAM-AS1	NR_120577.1	n.281-2609A>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESAM	ENST00000278927.10	c.35T>A	p.Leu12*	stop_gained	Exon 1 of 7	1	NM_138961.3	ENSP00000278927.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Pathogenic:1

Jan 01, 2023

Molecular Medicine, University of Pavia

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity Pathogenic:1

May 11, 2023

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	34
DANN	Benign	0.96
Eigen	Benign	-0.038
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.048	N
Vest4		0.45
GERP RS		0.28

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: chr11-124632016;