chr12-21526911-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_030572.4(SPX):​c.32C>T​(p.Thr11Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SPX
NM_030572.4 missense

Scores

2
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07815313).
BP6
Variant 12-21526911-C-T is Benign according to our data. Variant chr12-21526911-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3169773.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPXNM_030572.4 linkuse as main transcriptc.32C>T p.Thr11Ile missense_variant 2/6 ENST00000256969.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPXENST00000256969.7 linkuse as main transcriptc.32C>T p.Thr11Ile missense_variant 2/61 NM_030572.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 19, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.036
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.078
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.0
M
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.044
Sift
Benign
0.12
T
Sift4G
Benign
0.16
T
Polyphen
0.0
B
Vest4
0.29
MutPred
0.37
Gain of catalytic residue at L16 (P = 0);
MVP
0.040
MPC
0.90
ClinPred
0.16
T
GERP RS
1.8
Varity_R
0.041
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr12-21679845; API