19-53237388-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182609.4(ZNF677):​c.1339G>C​(p.Val447Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 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: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF677
NM_182609.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.30
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.035436988).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF677NM_182609.4 linkc.1339G>C p.Val447Leu 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.1339G>C p.Val447Leu missense_variant Exon 5 of 5 1 NM_182609.4 ENSP00000469391.1 Q86XU0
ZNF677ENST00000333952.8 linkc.1339G>C p.Val447Leu missense_variant Exon 3 of 3 2 ENSP00000334394.4 Q86XU0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251096
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135742
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461806
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1339G>C (p.V447L) alteration is located in exon 5 (coding exon 3) of the ZNF677 gene. This alteration results from a G to C substitution at nucleotide position 1339, causing the valine (V) at amino acid position 447 to be replaced by a leucine (L). 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
0.23
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.8
DANN
Benign
0.79
DEOGEN2
Benign
0.026
T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.00044
N
LIST_S2
Benign
0.13
.;T
M_CAP
Benign
0.00064
T
MetaRNN
Benign
0.035
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-0.68
N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.1
.;N
REVEL
Benign
0.018
Sift
Benign
0.30
.;T
Sift4G
Benign
0.31
T;T
Polyphen
0.0010
B;B
Vest4
0.024
MutPred
0.38
Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP
0.15
MPC
0.043
ClinPred
0.066
T
GERP RS
-3.2
Varity_R
0.066
gMVP
0.022

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: rs1189056850; hg19: chr19-53740641; API