3-113273180-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001378074.1(BOC):c.1073G>A(p.Arg358Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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: 5.25

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30244228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BOC	NM_001378074.1	c.1073G>A	p.Arg358Lys	missense_variant	8/20	ENST00000682979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BOC	ENST00000682979.1	c.1073G>A	p.Arg358Lys	missense_variant	8/20		NM_001378074.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250020 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135268

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.1073G>A (p.R358K) alteration is located in exon 8 (coding exon 6) of the BOC gene. This alteration results from a G to A substitution at nucleotide position 1073, causing the arginine (R) at amino acid position 358 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.0070	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.27	T;.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.37	N;N;N
MutationTaster	Benign	0.94	D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.080	N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.69	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.041	B;B;B
Vest4		0.52
MutPred		0.54		Gain of methylation at R358 (P = 0.0194);Gain of methylation at R358 (P = 0.0194);Gain of methylation at R358 (P = 0.0194);
MVP		0.82
MPC		0.36
ClinPred		0.89	D
GERP RS		4.0
Varity_R		0.12
gMVP		0.71

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: rs767316555; hg19: chr3-112992027;