chr20-23365248-G-C

Position:

• chr20-23365248-G-C

Variant summary

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

The NM_022482.5(GZF1):​c.865G>C​(p.Glu289Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GZF1 NM_022482.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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]

GZF1 (HGNC:):

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=0.090459555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GZF1	NM_022482.5	c.865G>C	p.Glu289Gln	missense_variant	2/6	ENST00000338121.10	NP_071927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GZF1	ENST00000338121.10	c.865G>C	p.Glu289Gln	missense_variant	2/6	1	NM_022482.5	ENSP00000338290.5
GZF1	ENST00000377051.2	c.865G>C	p.Glu289Gln	missense_variant	1/5	1		ENSP00000366250.2
GZF1	ENST00000461789.1	n.30G>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453546 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 722210

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.9
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.50	.;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.090	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.069
Sift	Benign	0.20	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.53	P;P
Vest4		0.085
MutPred		0.20		Loss of solvent accessibility (P = 0.0172);Loss of solvent accessibility (P = 0.0172);
MVP		0.24
MPC		0.67
ClinPred		0.15	T
GERP RS		4.0
Varity_R		0.035
gMVP		0.17

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: rs1555786618; hg19: chr20-23345885; COSMIC: COSV57636107; COSMIC: COSV57636107;