20-23364548-C-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_022482.5(GZF1):​c.165C>A​(p.Ala55Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000376 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

GZF1
NM_022482.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.425
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 20-23364548-C-A is Benign according to our data. Variant chr20-23364548-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1597899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.425 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000217 (33/152214) while in subpopulation AMR AF= 0.000589 (9/15278). AF 95% confidence interval is 0.000307. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GZF1NM_022482.5 linkc.165C>A p.Ala55Ala synonymous_variant Exon 2 of 6 ENST00000338121.10 NP_071927.1 Q9H116-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GZF1ENST00000338121.10 linkc.165C>A p.Ala55Ala synonymous_variant Exon 2 of 6 1 NM_022482.5 ENSP00000338290.5 Q9H116-1
GZF1ENST00000377051.2 linkc.165C>A p.Ala55Ala synonymous_variant Exon 1 of 5 1 ENSP00000366250.2 Q9H116-1
GZF1ENST00000424216.1 linkc.*19C>A downstream_gene_variant 5 ENSP00000410009.1 Q5JXG1

Frequencies

GnomAD3 genomes
AF:
0.000217
AC:
33
AN:
152214
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000215
AC:
54
AN:
251456
Hom.:
0
AF XY:
0.000250
AC XY:
34
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000308
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000393
AC:
574
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.000381
AC XY:
277
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.000358
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:
0.000469
Gnomad4 OTH exome
AF:
0.000530
GnomAD4 genome
AF:
0.000217
AC:
33
AN:
152214
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000396
Hom.:
1
Bravo
AF:
0.000272
EpiCase
AF:
0.000600
EpiControl
AF:
0.000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Dec 06, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
CADD
Benign
11
DANN
Benign
0.67

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146392173; hg19: chr20-23345185; COSMIC: COSV57636763; COSMIC: COSV57636763; API