rs10958476

chr8-56183249-T-C

Variant summary

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

The NM_002655.3(PLAG1):c.-321-3736A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,212 control chromosomes in the GnomAD database, including 2,297 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 0.16 (2297 hom., cov: 32)
• Consequence: PLAG1 NM_002655.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986

Genes affected

PLAG1 (HGNC:9045): (PLAG1 zinc finger) Pleomorphic adenoma gene 1 encodes a zinc finger protein with 2 putative nuclear localization signals. PLAG1, which is developmentally regulated, has been shown to be consistently rearranged in pleomorphic adenomas of the salivary glands. PLAG1 is activated by the reciprocal chromosomal translocations involving 8q12 in a subset of salivary gland pleomorphic adenomas. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAG1	NM_002655.3	c.-321-3736A>G		intron_variant		ENST00000316981.8
PLAG1	NM_001114634.2	c.-216-12060A>G		intron_variant
PLAG1	NM_001114635.2	c.-103-12060A>G		intron_variant
PLAG1	XM_017013576.2	c.-449-3736A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAG1	ENST00000316981.8	c.-321-3736A>G		intron_variant		1	NM_002655.3	P1
PLAG1	ENST00000429357.2	c.-216-12060A>G		intron_variant		1		P1
PLAG1	ENST00000423799.6	c.-103-12060A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24234 AN: 152094 Hom.: 2296 Cov.: 32

Gnomad AFR AF: 0.0657

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.159 AC: 24230 AN: 152212 Hom.: 2297 Cov.: 32 AF XY: 0.159 AC XY: 11851 AN XY: 74408

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.138

Alfa AF: 0.198 Hom.: 5452

Bravo AF: 0.146

Asia WGS AF: 0.172 AC: 598 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	7.5
Dann	Benign	0.91

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: rs10958476; hg19: chr8-57095808;