12-21526911-C-T

Variant names:

• chr12-21526911-C-T
• rs775231566
• NM_030572.4:c.32C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 13/20 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 3169773.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030572.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPX	NM_030572.4	MANE Select	c.32C>T	p.Thr11Ile	missense	Exon 2 of 6	NP_085049.1	Q9BT56

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPX	ENST00000256969.7	TSL:1 MANE Select	c.32C>T	p.Thr11Ile	missense	Exon 2 of 6	ENSP00000256969.2	Q9BT56
	SPX	ENST00000535033.5	TSL:2	c.-260C>T		upstream_gene	N/A	ENSP00000497284.1	A0A3B3ISF3
	SPX	ENST00000546199.1	TSL:4	n.-260C>T		upstream_gene	N/A	ENSP00000440877.1	F5GXE5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.6
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
PromoterAI		0.050	Neutral
Varity_R		0.041
gMVP		0.29
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs775231566; hg19: chr12-21679845;