rs372762092

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001040424.3(PRDM15):​c.2767G>C​(p.Glu923Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,112 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E923K) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000020 ( 1 hom., cov: 33)
Exomes š‘“: 0.000038 ( 0 hom. )

Consequence

PRDM15
NM_001040424.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.45
Variant links:
Genes affected
PRDM15 (HGNC:13999): (PR/SET domain 15) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and promoter-specific chromatin binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II; regulation of signal transduction; and regulation of stem cell division. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.050260127).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRDM15NM_001040424.3 linkc.2767G>C p.Glu923Gln missense_variant Exon 23 of 24 ENST00000398548.6 NP_001035514.2 P57071

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRDM15ENST00000398548.6 linkc.2767G>C p.Glu923Gln missense_variant Exon 23 of 24 1 NM_001040424.3 ENSP00000381556.2 P57071

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152196
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251416
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135892
show subpopulations
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 SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000376
AC:
55
AN:
1461798
Hom.:
0
Cov.:
32
AF XY:
0.0000536
AC XY:
39
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152314
Hom.:
1
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.013
.;.;T;T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.36
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.82
T;T;T;T
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.050
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.81
.;.;.;L
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.24
N;N;N;N
REVEL
Benign
0.044
Sift
Benign
0.25
T;T;T;T
Sift4G
Benign
0.99
T;T;T;T
Polyphen
0.060
.;.;.;B
Vest4
0.13
MutPred
0.35
.;.;.;Gain of MoRF binding (P = 0.0534);
MVP
0.068
MPC
0.44
ClinPred
0.033
T
GERP RS
4.0
Varity_R
0.047
gMVP
0.35

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: rs372762092; hg19: chr21-43223048; API