5-177992754-A-G

Position:

• chr5-177992754-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_006261.5(PROP1):​c.636T>C​(p.Pro212Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00055 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PROP1 NM_006261.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.371

Genes affected

PROP1 (HGNC:9455): (PROP paired-like homeobox 1) This gene encodes a paired-like homeodomain transcription factor in the developing pituitary gland. Expression occurs prior to and is required for expression of pou domain transcription factor 1, which is responsible for pituitary development and hormone expression. Mutations in this gene have been associated with combined pituitary hormone deficiency-2 as well as deficiencies in luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, and thyroid-stimulating hormone. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-177992754-A-G is Benign according to our data. Variant chr5-177992754-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 284436.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=-0.371 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROP1	NM_006261.5	c.636T>C	p.Pro212Pro	synonymous_variant	3/3	ENST00000308304.2	NP_006252.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROP1	ENST00000308304.2	c.636T>C	p.Pro212Pro	synonymous_variant	3/3	1	NM_006261.5	ENSP00000311290.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 261 AN: 18130 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00768

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.00976

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0340

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000553 AC: 162 AN: 292780 Hom.: 0 Cov.: 16 AF XY: 0.000636 AC XY: 96 AN XY: 150884

Gnomad4 AFR exome AF: 0.000122

Gnomad4 AMR exome AF: 0.000407

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000307

Gnomad4 FIN exome AF: 0.000596

Gnomad4 NFE exome AF: 0.000638

Gnomad4 OTH exome AF: 0.000351

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0143 AC: 260 AN: 18170 Hom.: 0 Cov.: 0 AF XY: 0.0145 AC XY: 128 AN XY: 8826

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.00766

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0146

Gnomad4 FIN AF: 0.00976

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0333

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 27, 2020	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 28, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.55

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: rs759632048; hg19: chr5-177419755;