chr12-120837839-T-C

Variant names:

• chr12-120837839-T-C
• rs7977343
• NM_139015.5:c.24-26953A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139015.5(SPPL3):​c.24-26953A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 147,444 control chromosomes in the GnomAD database, including 4,464 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 0.20 (4464 hom., cov: 31)
• Consequence: SPPL3 NM_139015.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPPL3	NM_139015.5	c.24-26953A>G		intron_variant	Intron 1 of 10	ENST00000353487.7	NP_620584.2
SPPL3	XM_011537925.3	c.24-26953A>G		intron_variant	Intron 1 of 10		XP_011536227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPPL3	ENST00000353487.7	c.24-26953A>G		intron_variant	Intron 1 of 10	1	NM_139015.5	ENSP00000288680.4
SPPL3	ENST00000536996.5	c.-88-26953A>G		intron_variant	Intron 2 of 8	5		ENSP00000442484.1
SPPL3	ENST00000543608.5	c.-88-26953A>G		intron_variant	Intron 1 of 6	3		ENSP00000437603.1
SPPL3	ENST00000543854.5	c.-146-26953A>G		intron_variant	Intron 1 of 5	5		ENSP00000439390.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 29389 AN: 147336 Hom.: 4458 Cov.: 31

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0606

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0850

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.200 AC: 29429 AN: 147444 Hom.: 4464 Cov.: 31 AF XY: 0.200 AC XY: 14391 AN XY: 72106

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0606

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.0850

Gnomad4 NFE AF: 0.0827

Gnomad4 OTH AF: 0.166

Alfa AF: 0.163 Hom.: 333

Bravo AF: 0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.35

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: rs7977343; hg19: chr12-121275642;