12-21527765-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_030572.4(SPX):c.184G>A(p.Asp62Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,571,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
SPX
NM_030572.4 missense
NM_030572.4 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 4.23
Genes affected
SPX (HGNC:28139): (spexin hormone) The protein encoded by this gene is a hormone involved in modulation of cardiovascular and renal function. It has also been shown in rats to cause weight loss. Several transcript variants have been found for this gene. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09679419).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPX | NM_030572.4 | c.184G>A | p.Asp62Asn | missense_variant | 4/6 | ENST00000256969.7 | |
SPX | NR_135187.2 | n.235G>A | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPX | ENST00000256969.7 | c.184G>A | p.Asp62Asn | missense_variant | 4/6 | 1 | NM_030572.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000496 AC: 9AN: 181474Hom.: 0 AF XY: 0.0000518 AC XY: 5AN XY: 96466
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GnomAD4 exome AF: 0.0000232 AC: 33AN: 1419460Hom.: 0 Cov.: 31 AF XY: 0.0000242 AC XY: 17AN XY: 701604
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74370
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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 | Oct 04, 2022 | The c.184G>A (p.D62N) alteration is located in exon 4 (coding exon 4) of the SPX gene. This alteration results from a G to A substitution at nucleotide position 184, causing the aspartic acid (D) at amino acid position 62 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;.
Polyphen
D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0352);.;
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