16-90062416-C-A

Position:

• chr16-90062416-C-A

Variant summary

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

The NM_001098173.2(PRDM7):​c.595G>T​(p.Asp199Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRDM7 NM_001098173.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM7	NM_001098173.2	c.595G>T	p.Asp199Tyr	missense_variant	7/11	ENST00000449207.8	NP_001091643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRDM7	ENST00000449207.8	c.595G>T	p.Asp199Tyr	missense_variant	7/11	1	NM_001098173.2	ENSP00000396732	P1
PRDM7	ENST00000564210.2	c.*117G>T		3_prime_UTR_variant, NMD_transcript_variant	4/6	5		ENSP00000457667
PRDM7	ENST00000568473.5	c.352-224G>T		intron_variant, NMD_transcript_variant		5		ENSP00000455390

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461822 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727214

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Aug 12, 2022

The c.595G>T (p.D199Y) alteration is located in exon 6 (coding exon 6) of the PRDM7 gene. This alteration results from a G to T substitution at nucleotide position 595, causing the aspartic acid (D) at amino acid position 199 to be replaced by a tyrosine (Y). 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	0.23
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.87	D;.
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	0.77	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-6.3	.;D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0010	.;D
Polyphen		1.0	D;D
Vest4		0.51
MutPred		0.52		Gain of phosphorylation at D199 (P = 0.0174);Gain of phosphorylation at D199 (P = 0.0174);
MVP		0.55
MPC		0.38
ClinPred		0.93	D
GERP RS		-0.52
Varity_R		0.46
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr16-90128824;