chrX-49831075-C-T

Variant names:

• chrX-49831075-C-T
• NM_007003.4:c.157C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007003.4(PAGE4):​c.157C>T​(p.Pro53Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: PAGE4 NM_007003.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.100
• Publications: 0 publications found

Genes affected

PAGE4 (HGNC:4108): (PAGE family member 4) This gene is a member of the GAGE family. The GAGE genes are expressed in a variety of tumors and in some fetal and reproductive tissues. This gene is strongly expressed in prostate and prostate cancer. It is also expressed in other male and female reproductive tissues including testis, fallopian tube, uterus, and placenta, as well as in testicular cancer and uterine cancer. The protein encoded by this gene shares sequence similarity with other GAGE/PAGE proteins, and also belongs to a family of CT (cancer-testis) antigens. The protein may play a role in benign and malignant prostate diseases. A related pseudogene is located on chromosome 7. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047038376).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007003.4. 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
	PAGE4	NM_007003.4	MANE Select	c.157C>T	p.Pro53Ser	missense	Exon 3 of 5	NP_008934.1	O60829
	PAGE4	NM_001318877.1		c.157C>T	p.Pro53Ser	missense	Exon 3 of 5	NP_001305806.1	O60829

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAGE4	ENST00000218068.7	TSL:1 MANE Select	c.157C>T	p.Pro53Ser	missense	Exon 3 of 5	ENSP00000218068.6	O60829
	PAGE4	ENST00000376141.5	TSL:5	c.157C>T	p.Pro53Ser	missense	Exon 3 of 5	ENSP00000365311.1	O60829
	PAGE4	ENST00000715210.1		c.157C>T	p.Pro53Ser	missense	Exon 3 of 5	ENSP00000520416.1	O60829

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1048495 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 323069

African (AFR) AF: 0.00 AC: 0 AN: 25221

American (AMR) AF: 0.00 AC: 0 AN: 31475

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18586

East Asian (EAS) AF: 0.00 AC: 0 AN: 29298

South Asian (SAS) AF: 0.00 AC: 0 AN: 49277

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39265

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4035

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 806915

Other (OTH) AF: 0.00 AC: 0 AN: 44423

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.052
DANN	Benign	0.36
DEOGEN2	Benign	0.0020	T
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.10
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.010
Sift	Benign	0.70	T
Sift4G	Benign	0.55	T
Polyphen		0.0030	B
Vest4		0.14
MutPred		0.22		Loss of catalytic residue at P52 (P = 0.012)
MVP		0.043
MPC		0.28
ClinPred		0.027	T
GERP RS		0.34
Varity_R		0.023
gMVP		0.013
Mutation Taster		=100/0	polymorphism

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

hg19: chrX-49595678;