NM_001098173.2:c.1276C>G

Variant names:

• chr16-90058492-G-C
• rs2037717840
• NM_001098173.2:c.1276C>G

Variant summary

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

The NM_001098173.2(PRDM7):​c.1276C>G​(p.Pro426Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRDM7 NM_001098173.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

Genes affected

PRDM7 (HGNC:9351): (PR/SET domain 7) This gene encodes a member of a family of proteins that may have roles in transcription and other nuclear processes. The encoded protein contains a KRAB (Kruppel-associated box) domain -A box and a SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain and may function as a histone methyltransferase. [provided by RefSeq, Aug 2013]

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=0.28124955).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098173.2. 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
	PRDM7	NM_001098173.2	MANE Select	c.1276C>G	p.Pro426Ala	missense	Exon 11 of 11	NP_001091643.1	Q9NQW5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM7	ENST00000449207.8	TSL:1 MANE Select	c.1276C>G	p.Pro426Ala	missense	Exon 11 of 11	ENSP00000396732.2	Q9NQW5-3
	PRDM7	ENST00000325921.10	TSL:1	n.516C>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.3
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.086	T
Polyphen		1.0	D
Vest4		0.16
MutPred		0.51		Gain of loop (P = 0.0045)
MVP		0.32
MPC		0.28
ClinPred		0.67	D
GERP RS		2.2
Varity_R		0.040
gMVP		0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs2037717840; hg19: chr16-90124900;