chr8-70069248-C-T

Variant names:

• chr8-70069248-C-T
• NM_024504.4:c.613G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024504.4(PRDM14):​c.613G>A​(p.Val205Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,452,254 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: PRDM14 NM_024504.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2900712).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024504.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM14	NM_024504.4	MANE Select	c.613G>A	p.Val205Ile	missense	Exon 2 of 8	NP_078780.1	Q9GZV8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM14	ENST00000276594.3	TSL:1 MANE Select	c.613G>A	p.Val205Ile	missense	Exon 2 of 8	ENSP00000276594.2	Q9GZV8
	PRDM14	ENST00000912626.1		c.613G>A	p.Val205Ile	missense	Exon 1 of 7	ENSP00000582685.1
	PRDM14	ENST00000912627.1		c.613G>A	p.Val205Ile	missense	Exon 2 of 8	ENSP00000582686.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1452254 Hom.: 0 Cov.: 32 AF XY: 0.00000554 AC XY: 4 AN XY: 721386

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 43936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25356

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.0000476 AC: 4 AN: 84058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107168

Other (OTH) AF: 0.00 AC: 0 AN: 59978

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.079
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.18
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.98	D
Vest4		0.31
MutPred		0.27		Gain of catalytic residue at V205 (P = 0.1006)
MVP		0.14
MPC		1.1
ClinPred		0.86	D
GERP RS		3.2
Varity_R		0.096
gMVP		0.42
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr8-70981483; COSMIC: COSV52571374; COSMIC: COSV52571374;