12-51245976-C-A

Position:

chr12-51245976-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001031628.2(SMAGP):c.259G>T(p.Ala87Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SMAGP
NM_001031628.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.122

Variant links:

Genes affected

SMAGP (HGNC:26918): (small cell adhesion glycoprotein) Located in cell junction; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMAGP links:

DAZAP2 (HGNC:2684): (DAZ associated protein 2) This gene encodes a proline-rich protein which interacts with the deleted in azoospermia (DAZ) and the deleted in azoospermia-like gene through the DAZ-like repeats. This protein also interacts with the transforming growth factor-beta signaling molecule SARA (Smad anchor for receptor activation), eukaryotic initiation factor 4G, and an E3 ubiquitinase that regulates its stability in splicing factor containing nuclear speckles. The encoded protein may function in various biological and pathological processes including spermatogenesis, cell signaling and transcription regulation, formation of stress granules during translation arrest, RNA splicing, and pathogenesis of multiple myeloma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

DAZAP2 links:

Genome browser will be placed here

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=0.026586026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMAGP	NM_001031628.2 linkuse as main transcript	c.259G>T	p.Ala87Ser	missense_variant	4/4	ENST00000603798.6	NP_001026798.1	Q0VAQ4
SMAGP	NM_001033873.1 linkuse as main transcript	c.259G>T	p.Ala87Ser	missense_variant	4/4		NP_001029045.1	Q0VAQ4
DAZAP2	NM_001136269.2 linkuse as main transcript	c.379-85C>A		intron_variant			NP_001129741.1	Q15038-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMAGP	ENST00000603798.6 linkuse as main transcript	c.259G>T	p.Ala87Ser	missense_variant	4/4	1	NM_001031628.2	ENSP00000475068.1		Q0VAQ4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000642

AC:

AN:

249178

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000464

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000666

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000579

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

Dec 20, 2023

The c.259G>T (p.A87S) alteration is located in exon 4 (coding exon 3) of the SMAGP gene. This alteration results from a G to T substitution at nucleotide position 259, causing the alanine (A) at amino acid position 87 to be replaced by a serine (S). 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

0.076

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.023

T;T;T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.71

.;.;T;T

M_CAP

Benign

0.075

MetaRNN

Benign

0.027

T;T;T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

.;N;.;.

REVEL

Benign

0.16

Sift

Benign

0.26

.;T;.;.

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.037

MutPred

0.17

Gain of phosphorylation at A87 (P = 0.0222);Gain of phosphorylation at A87 (P = 0.0222);Gain of phosphorylation at A87 (P = 0.0222);.;

MVP

0.040

MPC

0.14

ClinPred

0.28

GERP RS

1.9

Varity_R

0.088

gMVP

0.26

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