chr16-29816710-C-T

Position:

• chr16-29816710-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024516.4(PAGR1):​c.185C>T​(p.Ser62Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAGR1 NM_024516.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47

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]

ENSG00000280893 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09751928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAGR1	NM_024516.4	c.185C>T	p.Ser62Phe	missense_variant	1/3	ENST00000320330.8	NP_078792.1
MVP-DT	NR_186424.1	n.246+2830G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAGR1	ENST00000320330.8	c.185C>T	p.Ser62Phe	missense_variant	1/3	1	NM_024516.4	ENSP00000326519.6
ENSG00000280893	ENST00000609618.2	n.*126C>T		non_coding_transcript_exon_variant	4/6	5		ENSP00000476774.2
ENSG00000280893	ENST00000609618.2	n.*126C>T		3_prime_UTR_variant	4/6	5		ENSP00000476774.2
MVP-DT	ENST00000569039.5	n.245+2830G>A		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2023

The c.185C>T (p.S62F) alteration is located in exon 1 (coding exon 1) of the PAGR1 gene. This alteration results from a C to T substitution at nucleotide position 185, causing the serine (S) at amino acid position 62 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.048
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.043	D
Polyphen		0.22	B
Vest4		0.13
MutPred		0.15		Loss of phosphorylation at S62 (P = 9e-04);
MVP		0.068
ClinPred		0.62	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-29828031; COSMIC: COSV100232709; COSMIC: COSV100232709;