ESAM p.Ser21Arg

Variant names:

• chr11-124762094-T-G
• NM_138961.3:c.61A>C
• ESAM p.Ser21Arg

Your query was ambiguous. Multiple possible variants found:

• chr11-124762094-T-G
• chr11-124762092-A-T
• chr11-124762092-A-C
• chr11-124762092-ACT-GCG
• chr11-124762092-ACT-TCG
• chr11-124762092-ACT-CCG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138961.3(ESAM):​c.61A>C​(p.Ser21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ESAM NM_138961.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• 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-AS1 (HGNC:55558): (ESAM antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29404587).

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.61A>C	p.Ser21Arg	missense	Exon 1 of 7	NP_620411.2	Q96AP7-1
	ESAM-AS1	NR_120577.1		n.281-2635T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESAM	ENST00000278927.10	TSL:1 MANE Select	c.61A>C	p.Ser21Arg	missense	Exon 1 of 7	ENSP00000278927.5	Q96AP7-1
	ESAM	ENST00000417453.5	TSL:1	n.61A>C		non_coding_transcript_exon	Exon 1 of 7	ENSP00000389235.1	F8WDW9
	ESAM	ENST00000906451.1		c.61A>C	p.Ser21Arg	missense	Exon 1 of 8	ENSP00000576510.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458774 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725698

African (AFR) AF: 0.00 AC: 0 AN: 33168

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39122

South Asian (SAS) AF: 0.00 AC: 0 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110558

Other (OTH) AF: 0.00 AC: 0 AN: 60244

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.052
Eigen_PC	Benign	0.043
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.16
Sift	Benign	0.036	D
Sift4G	Benign	0.13	T
PromoterAI		0.034	Neutral
Varity_R		0.39
gMVP		0.68
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-124631990;