16-29821552-A-G

Variant names:

• chr16-29821552-A-G
• rs12149746
• NM_024516.4:c.*1798A>G

Variant summary

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

The NM_024516.4(PAGR1):​c.*1798A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 152,264 control chromosomes in the GnomAD database, including 70,155 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 0.96 (70155 hom., cov: 32)
• Consequence: PAGR1 NM_024516.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.766
• Publications: 3 publications found

Genes affected

PAGR1 (HGNC:28707): (PAXIP1 associated glutamate rich protein 1) Enables estrogen receptor binding activity. Involved in positive regulation of cell cycle G1/S phase transition; positive regulation of intracellular estrogen receptor signaling pathway; and positive regulation of transcription by RNA polymerase II. Located in nucleus. Part of MLL3/4 complex. [provided by Alliance of Genome Resources, Apr 2022]

MVP (HGNC:7531): (major vault protein) This gene encodes the major component of the vault complex. Vaults are multi-subunit ribonucleoprotein structures that may be involved in nucleo-cytoplasmic transport. The encoded protein may play a role in multiple cellular processes by regulating the MAP kinase, JAK/STAT and phosphoinositide 3-kinase/Akt signaling pathways. The encoded protein also plays a role in multidrug resistance, and expression of this gene may be a prognostic marker for several types of cancer. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

ENSG00000281348 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024516.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAGR1	NM_024516.4	MANE Select	c.*1798A>G		3_prime_UTR	Exon 3 of 3	NP_078792.1
	MVP	NM_005115.5	MANE Select	c.-36+1042A>G		intron	N/A	NP_005106.2
	MVP	NM_017458.3		c.-77+1042A>G		intron	N/A	NP_059447.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAGR1	ENST00000320330.8	TSL:1 MANE Select	c.*1798A>G		3_prime_UTR	Exon 3 of 3	ENSP00000326519.6
	MVP	ENST00000357402.10	TSL:1 MANE Select	c.-36+1042A>G		intron	N/A	ENSP00000349977.5
	ENSG00000281348	ENST00000562285.1	TSL:2	n.*148+1650A>G		intron	N/A	ENSP00000457363.1

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145765 AN: 152146 Hom.: 70101 Cov.: 32

Gnomad AFR AF: 0.862

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.973

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

GnomAD4 genome AF: 0.958 AC: 145876 AN: 152264 Hom.: 70155 Cov.: 32 AF XY: 0.958 AC XY: 71307 AN XY: 74464

African (AFR) AF: 0.862 AC: 35793 AN: 41514

American (AMR) AF: 0.985 AC: 15063 AN: 15294

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 0.937 AC: 4851 AN: 5178

South Asian (SAS) AF: 0.998 AC: 4815 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67997 AN: 68034

Other (OTH) AF: 0.973 AC: 2057 AN: 2114

Alfa AF: 0.979 Hom.: 30859

Bravo AF: 0.951

Asia WGS AF: 0.970 AC: 3371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.5
DANN	Benign	0.70
PhyloP100		0.77
PromoterAI		0.0042	Neutral
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: rs12149746; hg19: chr16-29832873;