rs779601690

chr4-120811438-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018699.4(PRDM5):c.877A>G(p.Lys293Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000627 in 1,435,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. K293K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: PRDM5 NM_018699.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.64

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18181598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRDM5	NM_018699.4	c.877A>G	p.Lys293Glu	missense_variant	8/16	ENST00000264808.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM5	ENST00000264808.8	c.877A>G	p.Lys293Glu	missense_variant	8/16	1	NM_018699.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000241 AC: 6 AN: 249222 Hom.: 0 AF XY: 0.0000371 AC XY: 5 AN XY: 134836

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: 0.000198

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000627 AC: 9 AN: 1435670 Hom.: 0 Cov.: 26 AF XY: 0.00000978 AC XY: 7 AN XY: 715468

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: 0.0000944

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000494 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Axenfeld-Rieger syndrome type 1 Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jun 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.36
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.048	T;.;.
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;T;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	0.93	D;D;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.097
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.10	B;B;.
Vest4		0.84
MutPred		0.46		Loss of methylation at K293 (P = 8e-04);.;.;
MVP		0.14
MPC		0.35
ClinPred		0.32	T
GERP RS		5.8
Varity_R		0.48
gMVP		0.35

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: rs779601690; hg19: chr4-121732593;