chr9-113369636-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017688.3(BSPRY):c.703G>A(p.Asp235Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
BSPRY
NM_017688.3 missense
NM_017688.3 missense
Scores
2
7
9
Clinical Significance
Conservation
PhyloP100: 4.31
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BSPRY | NM_017688.3 | c.703G>A | p.Asp235Asn | missense_variant | 6/6 | ENST00000374183.5 | |
BSPRY | NM_001317943.2 | c.718G>A | p.Asp240Asn | missense_variant | 6/6 | ||
BSPRY | NM_001317944.2 | c.578G>A | p.Arg193Gln | missense_variant | 5/5 | ||
BSPRY | XM_006717149.4 | c.700G>A | p.Asp234Asn | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BSPRY | ENST00000374183.5 | c.703G>A | p.Asp235Asn | missense_variant | 6/6 | 1 | NM_017688.3 | P1 | |
BSPRY | ENST00000462085.1 | n.616G>A | non_coding_transcript_exon_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248558Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134806
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461072Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726796
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2023 | The c.703G>A (p.D235N) alteration is located in exon 6 (coding exon 6) of the BSPRY gene. This alteration results from a G to A substitution at nucleotide position 703, causing the aspartic acid (D) at amino acid position 235 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Benign
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MutPred
Loss of disorder (P = 0.096);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at