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GeneBe

2-152664205-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001365597.4(PRPF40A):c.1938A>G(p.Ser646=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,610,484 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 14 hom., cov: 33)
Exomes 𝑓: 0.00070 ( 7 hom. )

Consequence

PRPF40A
NM_001365597.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.48
Variant links:
Genes affected
PRPF40A (HGNC:16463): (pre-mRNA processing factor 40 homolog A) Enables RNA binding activity. Involved in several processes, including cytoskeleton organization; regulation of cell shape; and regulation of cytokinesis. Located in nuclear matrix and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-152664205-T-C is Benign according to our data. Variant chr2-152664205-T-C is described in ClinVar as [Benign]. Clinvar id is 711345.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.48 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00593 (904/152318) while in subpopulation AFR AF= 0.0201 (837/41570). AF 95% confidence interval is 0.019. There are 14 homozygotes in gnomad4. There are 437 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 890 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRPF40ANM_001365597.4 linkuse as main transcriptc.1938A>G p.Ser646= synonymous_variant 17/26 ENST00000545856.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRPF40AENST00000545856.8 linkuse as main transcriptc.1938A>G p.Ser646= synonymous_variant 17/261 NM_001365597.4 P3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00585
AC:
890
AN:
152200
Hom.:
13
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0199
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00269
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:
0.0000882
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.00153
AC:
379
AN:
248280
Hom.:
3
AF XY:
0.00131
AC XY:
176
AN XY:
134754
show subpopulations
Gnomad AFR exome
AF:
0.0203
Gnomad AMR exome
AF:
0.00146
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000711
Gnomad OTH exome
AF:
0.000996
GnomAD4 exome
AF:
0.000704
AC:
1026
AN:
1458166
Hom.:
7
Cov.:
30
AF XY:
0.000620
AC XY:
450
AN XY:
725762
show subpopulations
Gnomad4 AFR exome
AF:
0.0229
Gnomad4 AMR exome
AF:
0.00168
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000523
Gnomad4 OTH exome
AF:
0.00189
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00593
AC:
904
AN:
152318
Hom.:
14
Cov.:
33
AF XY:
0.00587
AC XY:
437
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0201
Gnomad4 AMR
AF:
0.00275
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00899
Alfa
AF:
0.00275
Hom.:
4
Bravo
AF:
0.00685
Asia WGS
AF:
0.00318
AC:
11
AN:
3476
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
Cadd
Benign
5.3
Dann
Benign
0.65
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
4.0

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

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

Other links and lift over

dbSNP: rs113359796; hg19: chr2-153520719; API