rs387907051

Variant names:

• chr11-124923807-C-T
• rs387907051
• NM_152722.5:c.631G>A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_152722.5(HEPACAM):​c.631G>A​(p.Asp211Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HEPACAM NM_152722.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.91

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.9
• PP5: Variant 11-124923807-C-T is Pathogenic according to our data. Variant chr11-124923807-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 30917.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEPACAM	NM_152722.5	c.631G>A	p.Asp211Asn	missense_variant	Exon 3 of 7	ENST00000298251.5	NP_689935.2
HEPACAM	NM_001411043.1	c.631G>A	p.Asp211Asn	missense_variant	Exon 3 of 7		NP_001397972.1
HEPACAM	XM_005271449.3	c.631G>A	p.Asp211Asn	missense_variant	Exon 3 of 7		XP_005271506.1
LOC107984406	XR_001748429.3	n.335-19593C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEPACAM	ENST00000298251.5	c.631G>A	p.Asp211Asn	missense_variant	Exon 3 of 7	1	NM_152722.5	ENSP00000298251.4
HEPACAM	ENST00000703807.1	c.631G>A	p.Asp211Asn	missense_variant	Exon 3 of 7			ENSP00000515485.1
HEPACAM	ENST00000526273.1	n.403G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Megalencephalic leukoencephalopathy with subcortical cysts 2A Pathogenic:1

Apr 08, 2011

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.73	D
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.024	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.66		Loss of stability (P = 0.1717);
MVP		0.76
MPC		1.0
ClinPred		1.0	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.57
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs387907051; hg19: chr11-124793703;