11-124753833-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_138961.3(ESAM):​c.986G>A​(p.Gly329Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G329R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ESAM
NM_138961.3 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.88
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.17927709).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ESAMNM_138961.3 linkc.986G>A p.Gly329Asp missense_variant Exon 7 of 7 ENST00000278927.10 NP_620411.2 Q96AP7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ESAMENST00000278927.10 linkc.986G>A p.Gly329Asp missense_variant Exon 7 of 7 1 NM_138961.3 ENSP00000278927.5 Q96AP7-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152110
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000840
AC:
21
AN:
249928
Hom.:
0
AF XY:
0.0000814
AC XY:
11
AN XY:
135074
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000609
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461208
Hom.:
0
Cov.:
32
AF XY:
0.0000179
AC XY:
13
AN XY:
726882
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000582
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152110
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ExAC
AF:
0.0000659
AC:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.986G>A (p.G329D) alteration is located in exon 7 (coding exon 7) of the ESAM gene. This alteration results from a G to A substitution at nucleotide position 986, causing the glycine (G) at amino acid position 329 to be replaced by an aspartic acid (D). 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
-0.33
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T
Eigen
Benign
0.13
Eigen_PC
Benign
0.053
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.1
D
REVEL
Benign
0.12
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.040
D
Polyphen
0.99
D
Vest4
0.28
MutPred
0.26
Loss of sheet (P = 7e-04);
MVP
0.55
MPC
0.30
ClinPred
0.39
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.35
gMVP
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs747622641; hg19: chr11-124623729; API