11-124753833-C-G

Variant names:

• chr11-124753833-C-G
• rs747622641
• NM_138961.3:c.986G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138961.3(ESAM):​c.986G>C​(p.Gly329Ala) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G329D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ESAM NM_138961.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

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=0.15162283).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138961.3. 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
	ESAM	NM_138961.3	MANE Select	c.986G>C	p.Gly329Ala	missense	Exon 7 of 7	NP_620411.2	Q96AP7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESAM	ENST00000278927.10	TSL:1 MANE Select	c.986G>C	p.Gly329Ala	missense	Exon 7 of 7	ENSP00000278927.5	Q96AP7-1
	ESAM	ENST00000417453.5	TSL:1	n.*259G>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000389235.1	F8WDW9
	ESAM	ENST00000417453.5	TSL:1	n.*259G>C		3_prime_UTR	Exon 7 of 7	ENSP00000389235.1	F8WDW9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.79
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.030
Sift	Benign	0.21	T
Sift4G	Benign	0.21	T
Polyphen		0.25	B
Vest4		0.12
MutPred		0.22		Loss of sheet (P = 7e-04)
MVP		0.35
MPC		0.070
ClinPred		0.40	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.44
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs747622641; hg19: chr11-124623729;