chr12-21526958-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030572.4(SPX):​c.79G>C​(p.Ala27Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SPX
NM_030572.4 missense

Scores

1
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.24
Variant links:
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]

Genome browser will be placed here

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
SPXNM_030572.4 linkuse as main transcriptc.79G>C p.Ala27Pro missense_variant 2/6 ENST00000256969.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPXENST00000256969.7 linkuse as main transcriptc.79G>C p.Ala27Pro missense_variant 2/61 NM_030572.4 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251436
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135890
show subpopulations
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsMar 25, 2022The c.79G>C (p.A27P) alteration is located in exon 2 (coding exon 2) of the SPX gene. This alteration results from a G to C substitution at nucleotide position 79, causing the alanine (A) at amino acid position 27 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
Benign
0.14
BayesDel_addAF
Uncertain
0.047
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T
Eigen
Benign
0.046
Eigen_PC
Benign
-0.071
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.60
T
M_CAP
Benign
0.0083
T
MetaRNN
Uncertain
0.68
D
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
1.0
N
PROVEAN
Uncertain
-3.6
D
REVEL
Benign
0.24
Sift
Benign
0.080
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.97
D
Vest4
0.72
MutPred
0.40
Gain of catalytic residue at A27 (P = 0);
MVP
0.36
MPC
1.1
ClinPred
0.96
D
GERP RS
3.9
Varity_R
0.66
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780278792; hg19: chr12-21679892; API