Variant chr17-45846317-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_175882.3(SPPL2C):c.1411A>G(p.Ile471Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,976 control chromosomes in the GnomAD database, including 32,784 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.14 ( 2142 hom., cov: 33)

Exomes 𝑓: 0.19 ( 30642 hom. )

Consequence

SPPL2C
NM_175882.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.896

Variant links:

Genes affected

SPPL2C (HGNC:28902): (signal peptide peptidase like 2C) Enables protein homodimerization activity. Predicted to be involved in membrane protein proteolysis. Located in endoplasmic reticulum membrane. Is integral component of cytoplasmic side of endoplasmic reticulum membrane and integral component of lumenal side of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPPL2C links:

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

MAPT-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018708348).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPPL2C	NM_175882.3 linkuse as main transcript	c.1411A>G	p.Ile471Val	missense_variant	1/1	ENST00000329196.7	NP_787078.2
MAPT-AS1	NR_024559.1 linkuse as main transcript	n.35-2156T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPPL2C	ENST00000329196.7 linkuse as main transcript	c.1411A>G	p.Ile471Val	missense_variant	1/1		NM_175882.3	ENSP00000332488	P1
MAPT-AS1	ENST00000634876.2 linkuse as main transcript	n.183-2156T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21854

AN:

152070

Hom.:

2144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0742

Gnomad FIN

AF:

0.0652

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.186

GnomAD3 exomes

AF:

0.145

AC:

36513

AN:

251412

Hom.:

3543

AF XY:

0.149

AC XY:

20203

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0399

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.0762

Gnomad FIN exome

AF:

0.0677

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.193

AC:

282745

AN:

1461788

Hom.:

30642

Cov.:

108

AF XY:

0.191

AC XY:

138904

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0365

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.000882

Gnomad4 SAS exome

AF:

0.0797

Gnomad4 FIN exome

AF:

0.0721

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.144

AC:

21844

AN:

152188

Hom.:

2142

Cov.:

AF XY:

0.134

AC XY:

9998

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0430

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0742

Gnomad4 FIN

AF:

0.0652

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.204

Hom.:

7074

Bravo

AF:

0.148

TwinsUK

AF:

0.232

AC:

862

ALSPAC

AF:

0.239

AC:

923

ESP6500AA

AF:

0.0461

AC:

203

ESP6500EA

AF:

0.224

AC:

1928

ExAC

AF:

0.144

AC:

17517

Asia WGS

AF:

0.0310

AC:

110

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.39

DANN

Benign

0.44

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.46

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

0.17

REVEL

Benign

0.022

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0040

Vest4

0.0060

MPC

0.094

ClinPred

0.0010

GERP RS

0.83

Varity_R

0.026

gMVP

0.16

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over