Variant 8-70069703-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024504.4(PRDM14):c.158T>G(p.Phe53Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000919 in 1,564,712 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 4 hom. )

Consequence

PRDM14
NM_024504.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72

Variant links:

Genes affected

PRDM14 (HGNC:14001): (PR/SET domain 14) This gene encodes a member of the PRDI-BF1 and RIZ homology domain containing (PRDM) family of transcriptional regulators. The encoded protein may possess histone methyltransferase activity and plays a critical role in cell pluripotency by suppressing the expression of differentiation marker genes. Expression of this gene may play a role in breast cancer. [provided by RefSeq, Dec 2011]

PRDM14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019714803).

BS2

High AC in GnomAd4 at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM14	NM_024504.4 linkuse as main transcript	c.158T>G	p.Phe53Cys	missense_variant	2/8	ENST00000276594.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM14	ENST00000276594.3 linkuse as main transcript	c.158T>G	p.Phe53Cys	missense_variant	2/8	1	NM_024504.4	P1
PRDM14	ENST00000426346.1 linkuse as main transcript	c.158T>G	p.Phe53Cys	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000579

AC:

100

AN:

172830

Hom.:

AF XY:

0.000614

AC XY:

AN XY:

92806

show subpopulations

Gnomad AFR exome

AF:

0.000102

Gnomad AMR exome

AF:

0.000341

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000452

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000213

GnomAD4 exome

AF:

0.000959

AC:

1354

AN:

1412400

Hom.:

Cov.:

AF XY:

0.000991

AC XY:

692

AN XY:

698214

show subpopulations

Gnomad4 AFR exome

AF:

0.000278

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000507

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.000786

GnomAD4 genome

AF:

0.000552

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000944

Hom.:

Bravo

AF:

0.000446

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000701

AC:

ExAC

AF:

0.000352

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

Apr 23, 2024

The c.158T>G (p.F53C) alteration is located in exon 2 (coding exon 1) of the PRDM14 gene. This alteration results from a T to G substitution at nucleotide position 158, causing the phenylalanine (F) at amino acid position 53 to be replaced by a cysteine (C). 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.081

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.4

N;D

REVEL

Benign

0.11

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.015

D;.

Polyphen

0.98

D;.

Vest4

0.40

MVP

0.12

MPC

1.3

ClinPred

0.044

GERP RS

2.2

Varity_R

0.19

gMVP

0.54

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