16-90063639-A-T

Position:

• chr16-90063639-A-T

Variant summary

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

The NM_001098173.2(PRDM7):​c.481T>A​(p.Ser161Thr) 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: 33)
• Consequence: PRDM7 NM_001098173.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.884

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

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=0.098570466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM7	NM_001098173.2	c.481T>A	p.Ser161Thr	missense_variant	6/11	ENST00000449207.8	NP_001091643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM7	ENST00000449207.8	c.481T>A	p.Ser161Thr	missense_variant	6/11	1	NM_001098173.2	ENSP00000396732	P1
PRDM7	ENST00000564210.2	c.*31-1137T>A		intron_variant, NMD_transcript_variant		5		ENSP00000457667
PRDM7	ENST00000568473.5	c.352-1447T>A		intron_variant, NMD_transcript_variant		5		ENSP00000455390

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.481T>A (p.S161T) alteration is located in exon 5 (coding exon 5) of the PRDM7 gene. This alteration results from a T to A substitution at nucleotide position 481, causing the serine (S) at amino acid position 161 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.49	T;.
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.97	.;N
REVEL	Benign	0.029
Sift	Benign	0.34	.;T
Sift4G	Uncertain	0.049	.;D
Polyphen		0.64	P;P
Vest4		0.054
MutPred		0.21		Gain of catalytic residue at S161 (P = 0.0371);Gain of catalytic residue at S161 (P = 0.0371);
MVP		0.13
MPC		0.085
ClinPred		0.12	T
GERP RS		1.6
Varity_R		0.094
gMVP		0.19

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: rs2037820564; hg19: chr16-90130047;