X-37453318-C-T

Variant names:

• chrX-37453318-C-T
• rs150262063
• NM_001142395.2:c.354C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001142395.2(PRRG1):​c.354C>T​(p.Gly118Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,205,860 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 101 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., 12 hem., cov: 22)
  • Exomes 𝑓: 0.00021 (0 hom. 89 hem.)
• Consequence: PRRG1 NM_001142395.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.157
• Publications: 0 publications found

Genes affected

PRRG1 (HGNC:9469): (proline rich and Gla domain 1) This gene encodes a vitamin K-dependent, gamma-carboxyglutamic acid (Gla)-containing, single-pass transmembrane protein. This protein contains a Gla domain at the N-terminus, preceded by a propeptide sequence required for post-translational gamma-carboxylation of specific glutamic acid residues by a vitamin K-dependent gamma-carboxylase. The C-terminus is proline-rich containing PPXY and PXXP motifs found in a variety of signaling and cytoskeletal proteins. This gene is highly expressed in the spinal cord. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2010]

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant X-37453318-C-T is Benign according to our data. Variant chrX-37453318-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.157 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRG1	NM_001142395.2	c.354C>T	p.Gly118Gly	synonymous_variant	Exon 4 of 4	ENST00000378628.9	NP_001135867.1
PRRG1	NM_000950.3	c.354C>T	p.Gly118Gly	synonymous_variant	Exon 5 of 5		NP_000941.1
PRRG1	NM_001173489.2	c.354C>T	p.Gly118Gly	synonymous_variant	Exon 5 of 5		NP_001166960.1
PRRG1	NM_001173490.2	c.354C>T	p.Gly118Gly	synonymous_variant	Exon 4 of 4		NP_001166961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRG1	ENST00000378628.9	c.354C>T	p.Gly118Gly	synonymous_variant	Exon 4 of 4	1	NM_001142395.2	ENSP00000367894.4
ENSG00000250349	ENST00000465127.1	c.171+27318C>T		intron_variant	Intron 3 of 8	5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 45 AN: 110592 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000813

Gnomad OTH AF: 0.000677

GnomAD2 exomes AF: 0.000191 AC: 35 AN: 183448 AF XY: 0.000206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000125

Gnomad NFE exome AF: 0.000403

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000207 AC: 227 AN: 1095268 Hom.: 0 Cov.: 31 AF XY: 0.000247 AC XY: 89 AN XY: 360864

African (AFR) AF: 0.00 AC: 0 AN: 26341

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19364

East Asian (EAS) AF: 0.00 AC: 0 AN: 30191

South Asian (SAS) AF: 0.00 AC: 0 AN: 54089

European-Finnish (FIN) AF: 0.000148 AC: 6 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.000249 AC: 209 AN: 839402

Other (OTH) AF: 0.000261 AC: 12 AN: 46011

GnomAD4 genome AF: 0.000407 AC: 45 AN: 110592 Hom.: 0 Cov.: 22 AF XY: 0.000366 AC XY: 12 AN XY: 32812

African (AFR) AF: 0.0000330 AC: 1 AN: 30323

American (AMR) AF: 0.00 AC: 0 AN: 10312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2637

East Asian (EAS) AF: 0.00 AC: 0 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2575

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5915

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.000813 AC: 43 AN: 52881

Other (OTH) AF: 0.000677 AC: 1 AN: 1477

Alfa AF: 0.00189 Hom.: 9

Bravo AF: 0.000200

EpiCase AF: 0.000709

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PRRG1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.1
DANN	Benign	0.75
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150262063; hg19: chrX-37312571;