19-22757752-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001080409.3(ZNF99):ā€‹c.2157T>Cā€‹(p.Thr719=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 120,558 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 (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0040 ( 0 hom., cov: 31)
Exomes š‘“: 0.000017 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

ZNF99
NM_001080409.3 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -6.37
Variant links:
Genes affected
ZNF99 (HGNC:13175): (zinc finger protein 99) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.11).
BP6
Variant 19-22757752-A-G is Benign according to our data. Variant chr19-22757752-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2649652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-6.37 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF99NM_001080409.3 linkuse as main transcriptc.2157T>C p.Thr719= synonymous_variant 4/4 ENST00000596209.4 NP_001073878.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF99ENST00000596209.4 linkuse as main transcriptc.2157T>C p.Thr719= synonymous_variant 4/45 NM_001080409.3 ENSP00000472969 P1

Frequencies

GnomAD3 genomes
AF:
0.00401
AC:
483
AN:
120460
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00627
Gnomad AMI
AF:
0.00718
Gnomad AMR
AF:
0.00263
Gnomad ASJ
AF:
0.000682
Gnomad EAS
AF:
0.00995
Gnomad SAS
AF:
0.00621
Gnomad FIN
AF:
0.00705
Gnomad MID
AF:
0.0467
Gnomad NFE
AF:
0.00211
Gnomad OTH
AF:
0.00428
GnomAD3 exomes
AF:
0.0000372
AC:
9
AN:
242200
Hom.:
0
AF XY:
0.0000454
AC XY:
6
AN XY:
132082
show subpopulations
Gnomad AFR exome
AF:
0.0000694
Gnomad AMR exome
AF:
0.0000897
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000336
Gnomad FIN exome
AF:
0.0000488
Gnomad NFE exome
AF:
0.0000271
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000165
AC:
24
AN:
1453610
Hom.:
1
Cov.:
42
AF XY:
0.0000221
AC XY:
16
AN XY:
723408
show subpopulations
Gnomad4 AFR exome
AF:
0.0000919
Gnomad4 AMR exome
AF:
0.0000226
Gnomad4 ASJ exome
AF:
0.0000388
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000582
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000542
Gnomad4 OTH exome
AF:
0.000117
GnomAD4 genome
AF:
0.00401
AC:
483
AN:
120558
Hom.:
0
Cov.:
31
AF XY:
0.00389
AC XY:
231
AN XY:
59400
show subpopulations
Gnomad4 AFR
AF:
0.00628
Gnomad4 AMR
AF:
0.00255
Gnomad4 ASJ
AF:
0.000682
Gnomad4 EAS
AF:
0.00947
Gnomad4 SAS
AF:
0.00676
Gnomad4 FIN
AF:
0.00705
Gnomad4 NFE
AF:
0.00211
Gnomad4 OTH
AF:
0.00422
Alfa
AF:
0.0179
Hom.:
0
EpiCase
AF:
0.00
EpiControl
AF:
0.0000600

ClinVar

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

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2023ZNF99: BP4, BP7 -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.1
CADD
Benign
1.4
DANN
Benign
0.33

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: rs12980594; hg19: chr19-22940554; COSMIC: COSV68054657; API