chr8-70069613-C-G

Variant names:

• chr8-70069613-C-G
• NM_024504.4:c.248G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_024504.4(PRDM14):​c.248G>C​(p.Gly83Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRDM14 NM_024504.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.020347953).
• BP6: Variant 8-70069613-C-G is Benign according to our data. Variant chr8-70069613-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3424638.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM14	NM_024504.4	c.248G>C	p.Gly83Ala	missense_variant	Exon 2 of 8	ENST00000276594.3	NP_078780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM14	ENST00000276594.3	c.248G>C	p.Gly83Ala	missense_variant	Exon 2 of 8	1	NM_024504.4	ENSP00000276594.2
PRDM14	ENST00000426346.1	c.248G>C	p.Gly83Ala	missense_variant	Exon 2 of 2	3		ENSP00000408653.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 25, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.8
DANN	Benign	0.62
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.020	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.1	N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.73	N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;.
Polyphen		0.0	B;.
Vest4		0.037
MutPred		0.060		Loss of catalytic residue at L84 (P = 0.1395);Loss of catalytic residue at L84 (P = 0.1395);
MVP		0.22
MPC		0.42
ClinPred		0.040	T
GERP RS		2.5
Varity_R		0.031
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr8-70981848;