rs13273123

Variant names:

• chr8-56188232-A-G
• rs13273123
• NM_002655.3:c.-321-8719T>C

Variant summary

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

The NM_002655.3(PLAG1):​c.-321-8719T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,170 control chromosomes in the GnomAD database, including 1,794 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 0.14 (1794 hom., cov: 32)
• Consequence: PLAG1 NM_002655.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 28 publications found

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]

PLAG1 Gene-Disease associations (from GenCC):

• silver-russell syndrome 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAG1	NM_002655.3	c.-321-8719T>C		intron_variant	Intron 1 of 4	ENST00000316981.8	NP_002646.2
PLAG1	NM_001114634.2	c.-216-17043T>C		intron_variant	Intron 1 of 3		NP_001108106.1
PLAG1	NM_001114635.2	c.-103-17043T>C		intron_variant	Intron 1 of 2		NP_001108107.1
PLAG1	XM_017013576.2	c.-449-8719T>C		intron_variant	Intron 1 of 5		XP_016869065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAG1	ENST00000316981.8	c.-321-8719T>C		intron_variant	Intron 1 of 4	1	NM_002655.3	ENSP00000325546.3
PLAG1	ENST00000429357.2	c.-216-17043T>C		intron_variant	Intron 1 of 3	1		ENSP00000416537.2
PLAG1	ENST00000423799.6	c.-103-17043T>C		intron_variant	Intron 1 of 2	2		ENSP00000404067.2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21749 AN: 152052 Hom.: 1796 Cov.: 32

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0777

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.143 AC: 21752 AN: 152170 Hom.: 1794 Cov.: 32 AF XY: 0.141 AC XY: 10474 AN XY: 74422

African (AFR) AF: 0.0661 AC: 2746 AN: 41526

American (AMR) AF: 0.152 AC: 2319 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 963 AN: 3470

East Asian (EAS) AF: 0.0775 AC: 402 AN: 5188

South Asian (SAS) AF: 0.142 AC: 683 AN: 4814

European-Finnish (FIN) AF: 0.146 AC: 1542 AN: 10594

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12315 AN: 67978

Other (OTH) AF: 0.175 AC: 369 AN: 2112

Alfa AF: 0.170 Hom.: 7456

Bravo AF: 0.142

Asia WGS AF: 0.121 AC: 421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.6
DANN	Benign	0.52
PhyloP100		-0.30
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: rs13273123; hg19: chr8-57100791;