Genetic Variant SPPL2C:p.Ser542Ser (chr17-45846532-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_175882.3(SPPL2C):c.1626A>G(p.Ser542Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,612,276 control chromosomes in the GnomAD database, including 654,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.86 ( 56698 hom., cov: 33)

Exomes 𝑓: 0.90 ( 597376 hom. )

Consequence

SPPL2C
NM_175882.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.22

Publications

18 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=-2.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPPL2C	NM_175882.3 link	c.1626A>G	p.Ser542Ser	synonymous_variant	Exon 1 of 1	ENST00000329196.7	NP_787078.2	Q8IUH8
MAPT-AS1	NR_024559.1 link	n.35-2371T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPPL2C	ENST00000329196.7 link	c.1626A>G	p.Ser542Ser	synonymous_variant	Exon 1 of 1	6	NM_175882.3	ENSP00000332488.5		Q8IUH8

Frequencies

GnomAD3 genomes

AF:

0.859

AC:

130648

AN:

152076

Hom.:

56669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.731

Gnomad AMI

AF:

0.927

Gnomad AMR

AF:

0.915

Gnomad ASJ

AF:

0.894

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.972

Gnomad FIN

AF:

0.925

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.893

Gnomad OTH

AF:

0.860

GnomAD2 exomes

AF:

0.910

AC:

226911

AN:

249314

AF XY:

0.914

show subpopulations

Gnomad AFR exome

AF:

0.726

Gnomad AMR exome

AF:

0.941

Gnomad ASJ exome

AF:

0.899

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.926

Gnomad NFE exome

AF:

0.895

Gnomad OTH exome

AF:

0.914

GnomAD4 exome

AF:

0.904

AC:

1319444

AN:

1460082

Hom.:

597376

Cov.:

121

AF XY:

0.906

AC XY:

658159

AN XY:

726474

show subpopulations

African (AFR)

AF:

0.726

AC:

24294

AN:

33480

American (AMR)

AF:

0.939

AC:

41983

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.900

AC:

23524

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39691

AN:

39700

South Asian (SAS)

AF:

0.967

AC:

83409

AN:

86256

European-Finnish (FIN)

AF:

0.923

AC:

47680

AN:

51646

Middle Eastern (MID)

AF:

0.897

AC:

5173

AN:

5768

European-Non Finnish (NFE)

AF:

0.898

AC:

999094

AN:

1111994

Other (OTH)

AF:

0.904

AC:

54596

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

9890

19780

29669

39559

49449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21442

42884

64326

85768

107210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.859

AC:

130729

AN:

152194

Hom.:

56698

Cov.:

AF XY:

0.864

AC XY:

64302

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.731

AC:

30330

AN:

41486

American (AMR)

AF:

0.915

AC:

14002

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.894

AC:

3105

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5162

AN:

5164

South Asian (SAS)

AF:

0.972

AC:

4689

AN:

4826

European-Finnish (FIN)

AF:

0.925

AC:

9810

AN:

10608

Middle Eastern (MID)

AF:

0.871

AC:

256

AN:

294

European-Non Finnish (NFE)

AF:

0.893

AC:

60708

AN:

68016

Other (OTH)

AF:

0.862

AC:

1822

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

909

1817

2726

3634

4543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.889

Hom.:

47080

Bravo

AF:

0.854

Asia WGS

AF:

0.968

AC:

3366

AN:

3478

EpiCase

AF:

0.898

EpiControl

AF:

0.900

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.046

(source)

DANN

Benign

0.41

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over