chr17-48721857-C-T

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

17

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]
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]

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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
PRAC1NM_032391.3 linkc.118G>A p.Asp40Asn missense_variant Exon 2 of 2 ENST00000290294.5 NP_115767.1 Q96KF2
PRAC2XM_011524747.2 linkc.-84+984C>T intron_variant Intron 1 of 1 XP_011523049.1 D3DTV9
PRAC2XM_047435918.1 linkc.-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
PRAC1ENST00000290294.5 linkc.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.:
12
Cov.:
32
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.:
1
AF XY:
0.000817
AC XY:
65
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.:
13
Cov.:
30
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.:
12
Cov.:
32
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.:
1
Bravo
AF:
0.00631
ESP6500AA
AF:
0.0207
AC:
55
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00271
AC:
61
Asia WGS
AF:
0.00231
AC:
8
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
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.13
DANN
Benign
0.39
DEOGEN2
Benign
0.060
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0078
N
LIST_S2
Benign
0.29
T
MetaRNN
Benign
0.0041
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.88
N
REVEL
Benign
0.055
Sift
Benign
0.78
T
Sift4G
Benign
0.92
T
Polyphen
0.048
B
Vest4
0.070
MVP
0.030
MPC
0.024
ClinPred
0.00037
T
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.

Other links and lift over

dbSNP: rs116043950; hg19: chr17-46799219; API