NM_139015.5:c.24-32150T>C

Variant names:

• chr12-120843036-A-G
• rs10431387
• NM_139015.5:c.24-32150T>C

Variant summary

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

The NM_139015.5(SPPL3):​c.24-32150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,074 control chromosomes in the GnomAD database, including 4,524 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 0.19 (4524 hom., cov: 31)
• Consequence: SPPL3 NM_139015.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139015.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPPL3	NM_139015.5	MANE Select	c.24-32150T>C		intron	N/A	NP_620584.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPPL3	ENST00000353487.7	TSL:1 MANE Select	c.24-32150T>C		intron	N/A	ENSP00000288680.4	Q8TCT6-2
	SPPL3	ENST00000961961.1		c.24-32150T>C		intron	N/A	ENSP00000632020.1
	SPPL3	ENST00000855477.1		c.24-51479T>C		intron	N/A	ENSP00000525536.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29444 AN: 151954 Hom.: 4518 Cov.: 31

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.160

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29481 AN: 152074 Hom.: 4524 Cov.: 31 AF XY: 0.194 AC XY: 14446 AN XY: 74386

African (AFR) AF: 0.408 AC: 16904 AN: 41406

American (AMR) AF: 0.153 AC: 2336 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2083 AN: 5174

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4826

European-Finnish (FIN) AF: 0.0838 AC: 889 AN: 10606

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0803 AC: 5462 AN: 67996

Other (OTH) AF: 0.158 AC: 334 AN: 2112

Alfa AF: 0.136 Hom.: 964

Bravo AF: 0.212

Asia WGS AF: 0.312 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.70
PhyloP100		-0.41
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: rs10431387; hg19: chr12-121280839;