rs10958476

Variant names:

• chr8-56183249-T-C
• rs10958476
• NM_002655.3:c.-321-3736A>G

Variant summary

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

The NM_002655.3(PLAG1):​c.-321-3736A>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
• Publications: 40 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002655.3. 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
	PLAG1	NM_002655.3	MANE Select	c.-321-3736A>G		intron	N/A	NP_002646.2	Q6DJT9-1
	PLAG1	NM_001114634.2		c.-216-12060A>G		intron	N/A	NP_001108106.1	Q6DJT9-1
	PLAG1	NM_001114635.2		c.-103-12060A>G		intron	N/A	NP_001108107.1	Q6DJT9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAG1	ENST00000316981.8	TSL:1 MANE Select	c.-321-3736A>G		intron	N/A	ENSP00000325546.3	Q6DJT9-1
	PLAG1	ENST00000429357.2	TSL:1	c.-216-12060A>G		intron	N/A	ENSP00000416537.2	Q6DJT9-1
	PLAG1	ENST00000878031.1		c.-381-3736A>G		intron	N/A	ENSP00000548090.1

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

African (AFR) AF: 0.0656 AC: 2724 AN: 41534

American (AMR) AF: 0.120 AC: 1833 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3472

East Asian (EAS) AF: 0.196 AC: 1017 AN: 5182

South Asian (SAS) AF: 0.145 AC: 701 AN: 4828

European-Finnish (FIN) AF: 0.237 AC: 2505 AN: 10578

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14378 AN: 67998

Other (OTH) AF: 0.138 AC: 291 AN: 2114

Alfa AF: 0.196 Hom.: 10758

Bravo AF: 0.146

Asia WGS AF: 0.172 AC: 598 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.5
DANN	Benign	0.91
PhyloP100		-0.99
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: rs10958476; hg19: chr8-57095808;