1-71047514-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_198719.2(PTGER3):c.64A>C(p.Thr22Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,448,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PTGER3 NM_198719.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.328

Genes affected

PTGER3 (HGNC:9595): (prostaglandin E receptor 3) The protein encoded by this gene is a member of the G-protein coupled receptor family. This protein is one of four receptors identified for prostaglandin E2 (PGE2). This receptor may have many biological functions, which involve digestion, nervous system, kidney reabsorption, and uterine contraction activities. Studies of the mouse counterpart suggest that this receptor may also mediate adrenocorticotropic hormone response as well as fever generation in response to exogenous and endogenous stimuli. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

ZRANB2-AS1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03330183).
• BP6: Variant 1-71047514-T-G is Benign according to our data. Variant chr1-71047514-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2297485.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGER3	NM_198719.2	c.64A>C	p.Thr22Pro	missense_variant	1/4	ENST00000306666.10
ZRANB2-AS1	NR_038420.1	n.1009T>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGER3	ENST00000306666.10	c.64A>C	p.Thr22Pro	missense_variant	1/4	1	NM_198719.2	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1448414 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 719038

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000542

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	0.70
Dann	Benign	0.59
DEOGEN2	Benign	0.088	T;.;.;.;.;T;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.040	N
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.033	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.7	N;N;.;N;N;N;N;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.69	N;.;N;N;N;N;N;N;N
REVEL	Benign	0.0070
Sift	Benign	0.33	T;.;T;T;T;T;T;T;T
Sift4G	Benign	0.57	T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;.;B;.;B;B;.;.
Vest4		0.059
MutPred		0.25		Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);
MVP		0.12
MPC		0.92
ClinPred		0.59	D
GERP RS		1.2
Varity_R		0.10
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs1314974804; hg19: chr1-71513197;