3-113278222-G-A

Variant names:

• chr3-113278222-G-A
• rs1553745274
• NM_001378074.1:c.1670G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001378074.1(BOC):​c.1670G>A​(p.Gly557Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BOC NM_001378074.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.59
• Publications: 1 publications found

Genes affected

BOC (HGNC:17173): (BOC cell adhesion associated, oncogene regulated) The protein encoded by this gene is a member of the immunoglobulin/fibronectin type III repeat family. It is a component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells, and promotes myogenic differentiation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BOC	NM_001378074.1	c.1670G>A	p.Gly557Glu	missense_variant	Exon 10 of 20	ENST00000682979.1	NP_001365003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BOC	ENST00000682979.1	c.1670G>A	p.Gly557Glu	missense_variant	Exon 10 of 20		NM_001378074.1	ENSP00000507783.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Holoprosencephaly sequence Uncertain:1

May 10, 2017

Muenke lab, National Institutes of Health

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

Increased binding of Sonic hedgehog in transfected mouse cells compared to the normal human gene. Hedgehog signaling strength depends on receptor binding and is implicated in holoprosencephaly and other conditions of midline signaling. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D;.;D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	.;D;D
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.3	M;.;M
PhyloP100		9.6
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-6.4	D;D;D
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.92
MutPred		0.74		Loss of catalytic residue at A555 (P = 0.0231);.;Loss of catalytic residue at A555 (P = 0.0231);
MVP		0.88
MPC		0.97
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.86
gMVP		0.83
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs1553745274; hg19: chr3-112997069;