9-135564323-C-T

Variant names:

• chr9-135564323-C-T
• rs140935798
• NM_002571.4:c.390C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_002571.4(PAEP):​c.390C>T​(p.Thr130Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,551,422 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (17 hom.)
• Consequence: PAEP NM_002571.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.700
• Publications: 0 publications found

Genes affected

PAEP (HGNC:8573): (progestagen associated endometrial protein) This gene is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The encoded glycoprotein has been previously referred to as pregnancy-associated endometrial alpha-2-globulin, placental protein 14, and glycodelin, but has been officially named progestagen-associated endometrial protein. Three distinct forms, with identical protein backbones but different glycosylation profiles, are found in amniotic fluid, follicular fluid and seminal plasma of the reproductive system. These glycoproteins have distinct and essential roles in regulating a uterine environment suitable for pregnancy and in the timing and occurrence of the appropriate sequence of events in the fertilization process. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.027).
• BP6: Variant 9-135564323-C-T is Benign according to our data. Variant chr9-135564323-C-T is described in ClinVar as [Benign]. Clinvar id is 790270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.7 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAEP	NM_002571.4	c.390C>T	p.Thr130Thr	synonymous_variant	Exon 4 of 7	ENST00000479141.6	NP_002562.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAEP	ENST00000479141.6	c.390C>T	p.Thr130Thr	synonymous_variant	Exon 4 of 7	1	NM_002571.4	ENSP00000417898.1
PAEP	ENST00000371766.6	c.390C>T	p.Thr130Thr	synonymous_variant	Exon 4 of 7	1		ENSP00000360831.1

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 260 AN: 152194 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00218

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00291 AC: 461 AN: 158414 AF XY: 0.00352

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00491

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000129

Gnomad NFE exome AF: 0.00230

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00223 AC: 3118 AN: 1399110 Hom.: 17 Cov.: 31 AF XY: 0.00254 AC XY: 1756 AN XY: 690128

African (AFR) AF: 0.000189 AC: 6 AN: 31674

American (AMR) AF: 0.00126 AC: 45 AN: 35722

Ashkenazi Jewish (ASJ) AF: 0.00496 AC: 125 AN: 25182

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35878

South Asian (SAS) AF: 0.0109 AC: 863 AN: 79220

European-Finnish (FIN) AF: 0.000101 AC: 5 AN: 49366

Middle Eastern (MID) AF: 0.00482 AC: 23 AN: 4770

European-Non Finnish (NFE) AF: 0.00177 AC: 1912 AN: 1079324

Other (OTH) AF: 0.00238 AC: 138 AN: 57974

GnomAD4 genome AF: 0.00170 AC: 259 AN: 152312 Hom.: 2 Cov.: 33 AF XY: 0.00188 AC XY: 140 AN XY: 74478

African (AFR) AF: 0.000216 AC: 9 AN: 41572

American (AMR) AF: 0.00118 AC: 18 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4826

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00216 AC: 147 AN: 68028

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00258 Hom.: 0

Bravo AF: 0.00141

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs140935798; hg19: chr9-138456169;