11-124921418-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152722.5(HEPACAM):c.971A>C(p.Asn324Thr) 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. N324S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEPACAM NM_152722.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046315968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEPACAM	NM_152722.5	c.971A>C	p.Asn324Thr	missense_variant	7/7	ENST00000298251.5
LOC107984406	XR_001748429.3	n.335-21982T>G		intron_variant, non_coding_transcript_variant
HEPACAM	NM_001411043.1	c.1127A>C	p.Asn376Thr	missense_variant	7/7
HEPACAM	XM_005271449.3	c.968A>C	p.Asn323Thr	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEPACAM	ENST00000298251.5	c.971A>C	p.Asn324Thr	missense_variant	7/7	1	NM_152722.5	P1
HEPACAM	ENST00000703807.1	c.1127A>C	p.Asn376Thr	missense_variant	7/7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	14
Dann	Benign	0.58
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.029
Sift	Benign	0.21	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.068
MutPred		0.27		Gain of phosphorylation at N324 (P = 0.0026);
MVP		0.34
MPC		1.6
ClinPred		0.10	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.17

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: rs116102273; hg19: chr11-124791314;