12-21526911-C-T

Variant names:

• chr12-21526911-C-T
• NM_030572.4:c.32C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.57

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]

ACMG classification

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 rank	MANE	Protein	UniProt
SPX	NM_030572.4	c.32C>T	p.Thr11Ile	missense_variant	Exon 2 of 6	ENST00000256969.7	NP_085049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPX	ENST00000256969.7	c.32C>T	p.Thr11Ile	missense_variant	Exon 2 of 6	1	NM_030572.4	ENSP00000256969.2
SPX	ENST00000535033.5	c.-260C>T		upstream_gene_variant		2		ENSP00000497284.1
SPX	ENST00000546199.1	n.-260C>T		upstream_gene_variant		4		ENSP00000440877.1

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

Submissions by phenotype

not specified Benign:1

Dec 19, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This 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
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;