Variant 16-90062048-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098173.2(PRDM7):c.755G>A(p.Gly252Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,614,126 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

PRDM7
NM_001098173.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

Variant links:

Genes affected

PRDM7 (HGNC:9351): (PR/SET domain 7) This gene encodes a member of a family of proteins that may have roles in transcription and other nuclear processes. The encoded protein contains a KRAB (Kruppel-associated box) domain -A box and a SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain and may function as a histone methyltransferase. [provided by RefSeq, Aug 2013]

PRDM7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22159186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM7	NM_001098173.2 linkuse as main transcript	c.755G>A	p.Gly252Asp	missense_variant	8/11	ENST00000449207.8	NP_001091643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM7	ENST00000449207.8 linkuse as main transcript	c.755G>A	p.Gly252Asp	missense_variant	8/11	1	NM_001098173.2	ENSP00000396732	P1	Q9NQW5-3
PRDM7	ENST00000325921.10 linkuse as main transcript	n.278G>A		non_coding_transcript_exon_variant	1/3	1
PRDM7	ENST00000564210.2 linkuse as main transcript	c.*277G>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	5		ENSP00000457667
PRDM7	ENST00000568473.5 linkuse as main transcript	c.*79G>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	5		ENSP00000455390

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251466

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135912

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727248

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000594

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74374

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Feb 11, 2022

The c.755G>A (p.G252D) alteration is located in exon 7 (coding exon 7) of the PRDM7 gene. This alteration results from a G to A substitution at nucleotide position 755, causing the glycine (G) at amino acid position 252 to be replaced by an aspartic acid (D). 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

0.23

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

0.033

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.79

T;.

M_CAP

Benign

0.021

MetaRNN

Benign

0.22

T;T

MetaSVM

Uncertain

-0.073

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

0.54

N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.5

.;D

REVEL

Benign

0.13

Sift

Benign

0.060

.;T

Sift4G

Uncertain

0.011

.;D

Polyphen

1.0

D;D

Vest4

0.35

MutPred

0.29

Loss of glycosylation at S251 (P = 0.048);Loss of glycosylation at S251 (P = 0.048);

MVP

0.82

MPC

0.29

ClinPred

0.86

GERP RS

2.6

Varity_R

0.16

gMVP

0.41

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