chr12-120798455-C-T

Variant names:

• chr12-120798455-C-T
• rs1039302
• NM_139015.5:c.102-6898G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• Publications: 22 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPPL3	NM_139015.5	c.102-6898G>A		intron_variant	Intron 2 of 10	ENST00000353487.7	NP_620584.2
SPPL3	XM_011537925.3	c.102-6898G>A		intron_variant	Intron 2 of 10		XP_011536227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPPL3	ENST00000353487.7	c.102-6898G>A		intron_variant	Intron 2 of 10	1	NM_139015.5	ENSP00000288680.4

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36417 AN: 151952 Hom.: 5546 Cov.: 32

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

African (AFR) AF: 0.421 AC: 17432 AN: 41454

American (AMR) AF: 0.176 AC: 2694 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0734 AC: 255 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2080 AN: 5168

South Asian (SAS) AF: 0.242 AC: 1164 AN: 4818

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10568

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10599 AN: 68002

Other (OTH) AF: 0.207 AC: 437 AN: 2116

Alfa AF: 0.182 Hom.: 10490

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
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1039302; hg19: chr12-121236258;