chr9-113360619-G-C

Position:

• chr9-113360619-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017688.3(BSPRY):​c.413G>C​(p.Arg138Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BSPRY NM_017688.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.11

Genes affected

BSPRY (HGNC:18232): (B-box and SPRY domain containing) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in cell leading edge; membrane; and perinuclear region of cytoplasm. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BSPRY (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSPRY	NM_017688.3	c.413G>C	p.Arg138Pro	missense_variant	3/6	ENST00000374183.5	NP_060158.2
BSPRY	NM_001317943.2	c.413G>C	p.Arg138Pro	missense_variant	3/6		NP_001304872.1
BSPRY	NM_001317944.2	c.413G>C	p.Arg138Pro	missense_variant	3/5		NP_001304873.1
BSPRY	XM_006717149.4	c.413G>C	p.Arg138Pro	missense_variant	3/6		XP_006717212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSPRY	ENST00000374183.5	c.413G>C	p.Arg138Pro	missense_variant	3/6	1	NM_017688.3	ENSP00000363298.4
BSPRY	ENST00000462085.1	n.451G>C		non_coding_transcript_exon_variant	3/5	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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2024

The c.413G>C (p.R138P) alteration is located in exon 3 (coding exon 3) of the BSPRY gene. This alteration results from a G to C substitution at nucleotide position 413, causing the arginine (R) at amino acid position 138 to be replaced by a proline (P). 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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.34		Gain of glycosylation at R138 (P = 0.0241);
MVP		0.33
MPC		0.48
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.78
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-116122899;