Variant 12-21529007-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030572.4(SPX):c.215G>A(p.Arg72Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SPX
NM_030572.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

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]

SPX links:

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
SPX	NM_030572.4 linkuse as main transcript	c.215G>A	p.Arg72Gln	missense_variant	5/6	ENST00000256969.7
SPX	NR_135187.2 linkuse as main transcript	n.266G>A		non_coding_transcript_exon_variant	2/3
SPX	NR_135188.2 linkuse as main transcript	n.207G>A		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPX	ENST00000256969.7 linkuse as main transcript	c.215G>A	p.Arg72Gln	missense_variant	5/6	1	NM_030572.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251460

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135902

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

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

Feb 10, 2022

The c.215G>A (p.R72Q) alteration is located in exon 5 (coding exon 5) of the SPX gene. This alteration results from a G to A substitution at nucleotide position 215, causing the arginine (R) at amino acid position 72 to be replaced by a glutamine (Q). 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

0.097

BayesDel_addAF

Uncertain

0.094

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

PROVEAN

Uncertain

-2.9

D;.

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.039

D;.

Polyphen

1.0

D;.

Vest4

0.56

MutPred

0.31

Gain of catalytic residue at L68 (P = 0.0657);.;

MVP

0.15

MPC

0.81

ClinPred

0.99

GERP RS

4.9

Varity_R

0.59

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over