8-70069700-C-T

Variant summary

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

The NM_024504.4(PRDM14):​c.161G>A​(p.Arg54Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,561,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

PRDM14
NM_024504.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.223
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]

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=0.025170624).
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRDM14NM_024504.4 linkc.161G>A p.Arg54Gln missense_variant Exon 2 of 8 ENST00000276594.3 NP_078780.1 Q9GZV8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRDM14ENST00000276594.3 linkc.161G>A p.Arg54Gln missense_variant Exon 2 of 8 1 NM_024504.4 ENSP00000276594.2 Q9GZV8
PRDM14ENST00000426346.1 linkc.161G>A p.Arg54Gln missense_variant Exon 2 of 2 3 ENSP00000408653.1 C9JMM8

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000178
AC:
3
AN:
168416
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
90336
show subpopulations
Gnomad AFR exome
AF:
0.000322
Gnomad AMR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000639
AC:
9
AN:
1409504
Hom.:
0
Cov.:
32
AF XY:
0.00000287
AC XY:
2
AN XY:
696542
show subpopulations
Gnomad4 AFR exome
AF:
0.000280
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152308
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.000687
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000253
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 20, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.161G>A (p.R54Q) alteration is located in exon 2 (coding exon 1) of the PRDM14 gene. This alteration results from a G to A substitution at nucleotide position 161, causing the arginine (R) at amino acid position 54 to be replaced by a glutamine (Q). 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
0.12
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
12
DANN
Benign
0.95
DEOGEN2
Benign
0.040
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.66
T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.025
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;.
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.73
N;N
REVEL
Benign
0.066
Sift
Benign
0.22
T;T
Sift4G
Benign
0.14
T;.
Polyphen
0.013
B;.
Vest4
0.048
MVP
0.29
MPC
0.45
ClinPred
0.016
T
GERP RS
-7.5
Varity_R
0.064
gMVP
0.21

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: rs138348268; hg19: chr8-70981935; API