19-53237231-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182609.4(ZNF677):​c.1496G>A​(p.Arg499His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,340 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ZNF677
NM_182609.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.02
Variant links:
Genes affected
ZNF677 (HGNC:28730): (zinc finger protein 677) Predicted to enable DNA-binding transcription factor 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 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=0.14013118).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF677NM_182609.4 linkc.1496G>A p.Arg499His missense_variant Exon 5 of 5 ENST00000598513.6 NP_872415.1 Q86XU0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF677ENST00000598513.6 linkc.1496G>A p.Arg499His missense_variant Exon 5 of 5 1 NM_182609.4 ENSP00000469391.1 Q86XU0
ZNF677ENST00000333952.8 linkc.1496G>A p.Arg499His missense_variant Exon 3 of 3 2 ENSP00000334394.4 Q86XU0

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151824
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
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:
0.00
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250778
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135608
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1460516
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
726604
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151824
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74136
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000480
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 28, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1496G>A (p.R499H) alteration is located in exon 5 (coding exon 3) of the ZNF677 gene. This alteration results from a G to A substitution at nucleotide position 1496, causing the arginine (R) at amino acid position 499 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
2.3
DANN
Benign
0.74
DEOGEN2
Benign
0.038
T;T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.00073
N
LIST_S2
Benign
0.41
.;T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L;L
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.66
.;N
REVEL
Benign
0.13
Sift
Benign
0.59
.;T
Sift4G
Benign
0.58
T;T
Polyphen
1.0
D;D
Vest4
0.20
MutPred
0.50
Loss of MoRF binding (P = 0.0545);Loss of MoRF binding (P = 0.0545);
MVP
0.56
MPC
0.050
ClinPred
0.12
T
GERP RS
2.2
Varity_R
0.028
gMVP
0.023

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: rs761424787; hg19: chr19-53740484; API