4-120695124-A-T

Position:

• chr4-120695124-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018699.4(PRDM5):​c.1880T>A​(p.Val627Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRDM5 NM_018699.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.02

Genes affected

PRDM5 (HGNC:9349): (PR/SET domain 5) The protein encoded by this gene is a transcription factor of the PR-domain protein family. It contains a PR-domain and multiple zinc finger motifs. Transcription factors of the PR-domain family are known to be involved in cell differentiation and tumorigenesis. [provided by RefSeq, Jul 2008]

PRDM5 (HGNC:):

ACMG classification

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=0.043182284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM5	NM_018699.4	c.1880T>A	p.Val627Glu	missense_variant	16/16	ENST00000264808.8	NP_061169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM5	ENST00000264808.8	c.1880T>A	p.Val627Glu	missense_variant	16/16	1	NM_018699.4	ENSP00000264808.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiovascular phenotype Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.45	N;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.8	N;N
REVEL	Benign	0.084
Sift	Benign	1.0	T;T
Sift4G	Benign	0.81	T;T
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.34		Gain of disorder (P = 0.0537);.;
MVP		0.043
MPC		0.24
ClinPred		0.75	D
GERP RS		4.4
Varity_R		0.14
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-121616279;