NM_144773.4:c.*67T>A

Variant names:

• chr20-5301973-A-T
• rs3746681
• NM_144773.4:c.*67T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144773.4(PROKR2):​c.*67T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,417,880 control chromosomes in the GnomAD database, including 149,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (13900 hom., cov: 32)
  • Exomes 𝑓: 0.46 (135333 hom.)
• Consequence: PROKR2 NM_144773.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00300
• Publications: 3 publications found

Genes affected

PROKR2 (HGNC:15836): (prokineticin receptor 2) Prokineticins are secreted proteins that can promote angiogenesis and induce strong gastrointestinal smooth muscle contraction. The protein encoded by this gene is an integral membrane protein and G protein-coupled receptor for prokineticins. The encoded protein is similar in sequence to GPR73, another G protein-coupled receptor for prokineticins. [provided by RefSeq, Jul 2008]

PROKR2 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 3 with or without anosmia

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Laboratory for Molecular Medicine
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• septooptic dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 20-5301973-A-T is Benign according to our data. Variant chr20-5301973-A-T is described in ClinVar as Benign. ClinVar VariationId is 1291545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144773.4. 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
	PROKR2	NM_144773.4	MANE Select	c.*67T>A		3_prime_UTR	Exon 3 of 3	NP_658986.1	Q8NFJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROKR2	ENST00000678254.1	MANE Select	c.*67T>A		3_prime_UTR	Exon 3 of 3	ENSP00000504128.1	Q8NFJ6
	PROKR2	ENST00000217270.4	TSL:1	c.*67T>A		3_prime_UTR	Exon 3 of 3	ENSP00000217270.3	Q8NFJ6
	PROKR2	ENST00000678059.1		c.*67T>A		3_prime_UTR	Exon 3 of 3	ENSP00000503366.1	A0A7I2V3D2

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64596 AN: 151888 Hom.: 13877 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.459 AC: 581500 AN: 1265874 Hom.: 135333 AF XY: 0.461 AC XY: 291936 AN XY: 633054

African (AFR) AF: 0.360 AC: 10705 AN: 29714

American (AMR) AF: 0.347 AC: 14477 AN: 41722

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 10602 AN: 23796

East Asian (EAS) AF: 0.394 AC: 14957 AN: 37940

South Asian (SAS) AF: 0.503 AC: 39304 AN: 78144

European-Finnish (FIN) AF: 0.458 AC: 21485 AN: 46906

Middle Eastern (MID) AF: 0.453 AC: 2442 AN: 5392

European-Non Finnish (NFE) AF: 0.467 AC: 442835 AN: 948518

Other (OTH) AF: 0.459 AC: 24693 AN: 53742

GnomAD4 genome AF: 0.425 AC: 64669 AN: 152006 Hom.: 13900 Cov.: 32 AF XY: 0.426 AC XY: 31670 AN XY: 74298

African (AFR) AF: 0.364 AC: 15107 AN: 41446

American (AMR) AF: 0.374 AC: 5717 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1529 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2279 AN: 5172

South Asian (SAS) AF: 0.510 AC: 2450 AN: 4806

European-Finnish (FIN) AF: 0.462 AC: 4886 AN: 10570

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31368 AN: 67944

Other (OTH) AF: 0.426 AC: 897 AN: 2108

Alfa AF: 0.440 Hom.: 1852

Bravo AF: 0.415

Asia WGS AF: 0.426 AC: 1479 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.1
DANN	Benign	0.89
PhyloP100		0.0030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3746681; hg19: chr20-5282619; COSMIC: COSV54085684;