17-48721857-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032391.3(PRAC1):c.118G>A(p.Asp40Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,541,592 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 13 hom. )

Consequence

PRAC1
NM_032391.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.455

Variant links:

Genes affected

PRAC1 (HGNC:30591): (PRAC1 small nuclear protein) This gene is reported to be specifically expressed in prostate, rectum and distal colon. Sequence analysis suggests that it may play a regulatory role in the nucleus. [provided by RefSeq, Jul 2008]

PRAC1 links:

PRAC2 (HGNC:30143): (PRAC2 small nuclear protein) This gene is highly expressed in prostate, rectum, colon, and testis. This gene may produce a non-coding RNA or may encode a short protein that might localize to the nucleus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

PRAC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004066527).

BP6

Variant 17-48721857-C-T is Benign according to our data. Variant chr17-48721857-C-T is described in ClinVar as [Benign]. Clinvar id is 777200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00581 (885/152354) while in subpopulation AFR AF= 0.0204 (848/41572). AF 95% confidence interval is 0.0193. There are 12 homozygotes in gnomad4. There are 419 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRAC1	NM_032391.3 link	c.118G>A	p.Asp40Asn	missense_variant	Exon 2 of 2	ENST00000290294.5	NP_115767.1	Q96KF2
PRAC2	XM_011524747.2 link	c.-84+984C>T		intron_variant	Intron 1 of 1		XP_011523049.1	D3DTV9
PRAC2	XM_047435918.1 link	c.-83-2471C>T		intron_variant	Intron 1 of 1		XP_047291874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRAC1	ENST00000290294.5 link	c.118G>A	p.Asp40Asn	missense_variant	Exon 2 of 2	1	NM_032391.3	ENSP00000290294.3		Q96KF2

Frequencies

GnomAD3 genomes

AF:

0.00582

AC:

886

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00137

AC:

207

AN:

150952

Hom.:

AF XY:

0.000817

AC XY:

AN XY:

79534

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.000827

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000452

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000350

Gnomad OTH exome

AF:

0.000232

GnomAD4 exome

AF:

0.000626

AC:

870

AN:

1389238

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

379

AN XY:

684856

show subpopulations

Gnomad4 AFR exome

AF:

0.0218

Gnomad4 AMR exome

AF:

0.000826

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000186

Gnomad4 OTH exome

AF:

0.00155

GnomAD4 genome

AF:

0.00581

AC:

885

AN:

152354

Hom.:

Cov.:

AF XY:

0.00562

AC XY:

419

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0204

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00631

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00271

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.13

DANN

Benign

0.39

DEOGEN2

Benign

0.060

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.88

REVEL

Benign

0.055

Sift

Benign

0.78

Sift4G

Benign

0.92

Polyphen

0.048

Vest4

0.070

MVP

0.030

MPC

0.024

ClinPred

0.00037

GERP RS

-0.71

Varity_R

0.044

gMVP

0.0017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over