17-45846532-A-G

Position:

• chr17-45846532-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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]

MAPT-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SPPL2C	NM_175882.3	c.1626A>G	p.Ser542Ser	synonymous_variant	1/1	ENST00000329196.7	NP_787078.2
MAPT-AS1	NR_024559.1	n.35-2371T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPPL2C	ENST00000329196.7	c.1626A>G	p.Ser542Ser	synonymous_variant	1/1	6	NM_175882.3	ENSP00000332488.5

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130648 AN: 152076 Hom.: 56669 Cov.: 33

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

GnomAD3 exomes AF: 0.910 AC: 226911 AN: 249314 Hom.: 103714 AF XY: 0.914 AC XY: 123454 AN XY: 135102

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 SAS exome AF: 0.967

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

Gnomad4 AFR exome AF: 0.726

Gnomad4 AMR exome AF: 0.939

Gnomad4 ASJ exome AF: 0.900

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.967

Gnomad4 FIN exome AF: 0.923

Gnomad4 NFE exome AF: 0.898

Gnomad4 OTH exome AF: 0.904

GnomAD4 genome AF: 0.859 AC: 130729 AN: 152194 Hom.: 56698 Cov.: 33 AF XY: 0.864 AC XY: 64302 AN XY: 74424

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.915

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.972

Gnomad4 FIN AF: 0.925

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.862

Alfa AF: 0.892 Hom.: 32731

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
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs171443; hg19: chr17-43923898; COSMIC: COSV61293348; COSMIC: COSV61293348;