12-120798455-C-T

Variant summary

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

The NM_139015.5(SPPL3):​c.102-6898G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,070 control chromosomes in the GnomAD database, including 5,551 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 0.24 ( 5551 hom., cov: 32)

Consequence

SPPL3
NM_139015.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.193
Variant links:
Genes affected
SPPL3 (HGNC:30424): (signal peptide peptidase like 3) Enables aspartic endopeptidase activity, intramembrane cleaving and protein homodimerization activity. Involved in several processes, including T cell receptor signaling pathway; positive regulation of calcineurin-NFAT signaling cascade; and positive regulation of protein dephosphorylation. Located in Golgi-associated vesicle membrane; plasma membrane; and rough endoplasmic reticulum. 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]

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 (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SPPL3NM_139015.5 linkuse as main transcriptc.102-6898G>A intron_variant ENST00000353487.7 NP_620584.2 Q8TCT6-2Q9UG23
SPPL3XM_011537925.3 linkuse as main transcriptc.102-6898G>A intron_variant XP_011536227.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SPPL3ENST00000353487.7 linkuse as main transcriptc.102-6898G>A intron_variant 1 NM_139015.5 ENSP00000288680.4 Q8TCT6-2

Frequencies

GnomAD3 genomes
AF:
0.240
AC:
36417
AN:
151952
Hom.:
5546
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.421
Gnomad AMI
AF:
0.149
Gnomad AMR
AF:
0.176
Gnomad ASJ
AF:
0.0734
Gnomad EAS
AF:
0.403
Gnomad SAS
AF:
0.242
Gnomad FIN
AF:
0.153
Gnomad MID
AF:
0.133
Gnomad NFE
AF:
0.156
Gnomad OTH
AF:
0.209
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.240
AC:
36455
AN:
152070
Hom.:
5551
Cov.:
32
AF XY:
0.237
AC XY:
17633
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.421
Gnomad4 AMR
AF:
0.176
Gnomad4 ASJ
AF:
0.0734
Gnomad4 EAS
AF:
0.402
Gnomad4 SAS
AF:
0.242
Gnomad4 FIN
AF:
0.153
Gnomad4 NFE
AF:
0.156
Gnomad4 OTH
AF:
0.207
Alfa
AF:
0.167
Hom.:
5684
Bravo
AF:
0.251
Asia WGS
AF:
0.318
AC:
1105
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.93
DANN
Benign
0.83

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.

Other links and lift over

dbSNP: rs1039302; hg19: chr12-121236258; API