20-23364432-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022482.5(GZF1):c.49C>T(p.Leu17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 1,611,752 control chromosomes in the GnomAD database, including 2,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (1129 hom., cov: 33)
  • Exomes 𝑓: 0.028 (1749 hom.)
• Consequence: GZF1 NM_022482.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.62

Genes affected

GZF1 (HGNC:15808): (GDNF inducible zinc finger protein 1) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 20-23364432-C-T is Benign according to our data. Variant chr20-23364432-C-T is described in ClinVar as [Benign]. Clinvar id is 1249326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GZF1	NM_022482.5	c.49C>T	p.Leu17=	synonymous_variant	2/6	ENST00000338121.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GZF1	ENST00000338121.10	c.49C>T	p.Leu17=	synonymous_variant	2/6	1	NM_022482.5	P1
GZF1	ENST00000377051.2	c.49C>T	p.Leu17=	synonymous_variant	1/5	1		P1
GZF1	ENST00000424216.1	c.49C>T	p.Leu17=	synonymous_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12041 AN: 152144 Hom.: 1117 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0664

GnomAD3 exomes AF: 0.0441 AC: 11027 AN: 249948 Hom.: 649 AF XY: 0.0434 AC XY: 5857 AN XY: 135056

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.0192

Gnomad ASJ exome AF: 0.0316

Gnomad EAS exome AF: 0.0747

Gnomad SAS exome AF: 0.0878

Gnomad FIN exome AF: 0.0125

Gnomad NFE exome AF: 0.0174

Gnomad OTH exome AF: 0.0358

GnomAD4 exome AF: 0.0276 AC: 40232 AN: 1459490 Hom.: 1749 Cov.: 31 AF XY: 0.0291 AC XY: 21097 AN XY: 725758

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.0219

Gnomad4 ASJ exome AF: 0.0322

Gnomad4 EAS exome AF: 0.0852

Gnomad4 SAS exome AF: 0.0857

Gnomad4 FIN exome AF: 0.0134

Gnomad4 NFE exome AF: 0.0148

Gnomad4 OTH exome AF: 0.0409

GnomAD4 genome AF: 0.0795 AC: 12099 AN: 152262 Hom.: 1129 Cov.: 33 AF XY: 0.0779 AC XY: 5797 AN XY: 74452

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.0781

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0403 Hom.: 318

Bravo AF: 0.0873

Asia WGS AF: 0.0730 AC: 255 AN: 3478

EpiCase AF: 0.0206

EpiControl AF: 0.0197

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	12
Dann	Benign	0.41

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: rs6076060; hg19: chr20-23345069; COSMIC: COSV57635908; COSMIC: COSV57635908;