Variant 21-41801274-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_001040424.3(PRDM15):c.3392C>T(p.Ala1131Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,543,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

PRDM15
NM_001040424.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07

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]

PRDM15 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, PRDM15

BP4

Computational evidence support a benign effect (MetaRNN=0.010563314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM15	NM_001040424.3 linkuse as main transcript	c.3392C>T	p.Ala1131Val	missense_variant	24/24	ENST00000398548.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM15	ENST00000398548.6 linkuse as main transcript	c.3392C>T	p.Ala1131Val	missense_variant	24/24	1	NM_001040424.3	P2

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

GnomAD3 exomes

AF:

0.000156

AC:

AN:

192364

Hom.:

AF XY:

0.000176

AC XY:

AN XY:

102312

show subpopulations

Gnomad AFR exome

AF:

0.00149

Gnomad AMR exome

AF:

0.000112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000667

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000920

AC:

128

AN:

1391264

Hom.:

Cov.:

AF XY:

0.0000877

AC XY:

AN XY:

684092

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000761

Gnomad4 OTH exome

AF:

0.000105

GnomAD4 genome

AF:

0.000414

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.0000653

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:

0.00

Alfa

AF:

0.0440

Hom.:

329

Bravo

AF:

0.000442

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000184

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.4490C>T (p.A1497V) alteration is located in exon 31 (coding exon 31) of the PRDM15 gene. This alteration results from a C to T substitution at nucleotide position 4490, causing the alanine (A) at amino acid position 1497 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.55

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.28

T;T;T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.21

N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.033

D;D;T;D

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.49

.;.;.;P

Vest4

0.20

MVP

0.043

MPC

0.42

ClinPred

0.033

GERP RS

3.6

Varity_R

0.025

gMVP

0.42

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.

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