4-120695200-C-T

Variant names:

• chr4-120695200-C-T
• rs1159152264
• NM_018699.4:c.1804G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018699.4(PRDM5):​c.1804G>A​(p.Ala602Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRDM5 NM_018699.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.42

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM5	NM_018699.4	c.1804G>A	p.Ala602Thr	missense_variant	Exon 16 of 16	ENST00000264808.8	NP_061169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM5	ENST00000264808.8	c.1804G>A	p.Ala602Thr	missense_variant	Exon 16 of 16	1	NM_018699.4	ENSP00000264808.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250898 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135600

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461368 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726984

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiovascular phenotype Uncertain:1

Sep 16, 2020

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.A602T variant (also known as c.1804G>A), located in coding exon 16 of the PRDM5 gene, results from a G to A substitution at nucleotide position 1804. The alanine at codon 602 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.016	T;.
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.72	N;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.78	N;N
REVEL	Benign	0.23
Sift	Benign	0.082	T;T
Sift4G	Benign	0.41	T;T
Polyphen		1.0	D;D
Vest4		0.58
MutPred		0.29		Loss of glycosylation at P597 (P = 0.079);.;
MVP		0.38
MPC		0.63
ClinPred		0.77	D
GERP RS		5.6
Varity_R		0.26
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

Other links and lift over

dbSNP: rs1159152264; hg19: chr4-121616355;