11-124923786-T-A

Position:

• chr11-124923786-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The ENST00000298251.5(HEPACAM):​c.652A>T​(p.Met218Leu) 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. 15/21 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. M218V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEPACAM ENST00000298251.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

Genes affected

HEPACAM (HGNC:26361): (hepatic and glial cell adhesion molecule) The protein encoded by this gene is a single-pass type I membrane protein that localizes to the cytoplasmic side of the cell membrane. The encoded protein acts as a homodimer and is involved in cell motility and cell-matrix interactions. The expression of this gene is downregulated or undetectable in many cancer cell lines, so this may be a tumor suppressor gene. [provided by RefSeq, Jul 2011]

LOC107984406 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a topological_domain Extracellular (size 206) in uniprot entity HECAM_HUMAN there are 11 pathogenic changes around while only 4 benign (73%) in ENST00000298251.5
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06283319).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEPACAM	NM_152722.5	c.652A>T	p.Met218Leu	missense_variant	3/7	ENST00000298251.5	NP_689935.2
LOC107984406	XR_001748429.3	n.335-19614T>A		intron_variant, non_coding_transcript_variant
HEPACAM	NM_001411043.1	c.652A>T	p.Met218Leu	missense_variant	3/7		NP_001397972.1
HEPACAM	XM_005271449.3	c.652A>T	p.Met218Leu	missense_variant	3/7		XP_005271506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEPACAM	ENST00000298251.5	c.652A>T	p.Met218Leu	missense_variant	3/7	1	NM_152722.5	ENSP00000298251	P1
HEPACAM	ENST00000703807.1	c.652A>T	p.Met218Leu	missense_variant	3/7			ENSP00000515485
HEPACAM	ENST00000526273.1	n.424A>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.87
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.49	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.014
Sift	Benign	0.76	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.33		Loss of phosphorylation at Y215 (P = 0.0909);
MVP		0.10
MPC		0.29
ClinPred		0.083	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.32

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

Other links and lift over

dbSNP: rs10790715; hg19: chr11-124793682;