chr16-90062468-A-G

Position:

• chr16-90062468-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001098173.2(PRDM7):​c.543T>C​(p.Tyr181Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,614,110 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00092 (6 hom.)
• Consequence: PRDM7 NM_001098173.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.161

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 16-90062468-A-G is Benign according to our data. Variant chr16-90062468-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2647149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.161 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRDM7	NM_001098173.2	c.543T>C	p.Tyr181Tyr	synonymous_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.543T>C	p.Tyr181Tyr	synonymous_variant	7/11	1	NM_001098173.2	ENSP00000396732.2
PRDM7	ENST00000564210.2	n.*65T>C		non_coding_transcript_exon_variant	4/6	5		ENSP00000457667.1
PRDM7	ENST00000564210.2	n.*65T>C		3_prime_UTR_variant	4/6	5		ENSP00000457667.1
PRDM7	ENST00000568473.5	n.352-276T>C		intron_variant		5		ENSP00000455390.1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 161 AN: 152134 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00159 AC: 398 AN: 249542 Hom.: 1 AF XY: 0.00150 AC XY: 203 AN XY: 135382

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.000579

Gnomad ASJ exome AF: 0.0220

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.000925 AC: 1352 AN: 1461858 Hom.: 6 Cov.: 33 AF XY: 0.000932 AC XY: 678 AN XY: 727232

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000581

Gnomad4 ASJ exome AF: 0.0235

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000521

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00106 AC: 161 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.000846 AC XY: 63 AN XY: 74442

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00209 Hom.: 1

Bravo AF: 0.00129

EpiCase AF: 0.00169

EpiControl AF: 0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

PRDM7: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.38
DANN	Benign	0.21

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: rs188033705; hg19: chr16-90128876;