7-64077672-C-T

Variant summary

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

The NM_001159522.3(ZNF727):​c.623C>T​(p.Ala208Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF727
NM_001159522.3 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.567
Variant links:
Genes affected
ZNF727 (HGNC:22785): (zinc finger protein 727) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.08439931).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF727NM_001159522.3 linkc.623C>T p.Ala208Val missense_variant Exon 4 of 4 ENST00000456806.3 NP_001152994.1 A8MUV8
ZNF727XM_017012225.3 linkc.527C>T p.Ala176Val missense_variant Exon 3 of 3 XP_016867714.1
ZNF727XR_242241.4 linkn.811C>T non_coding_transcript_exon_variant Exon 4 of 5
ZNF727XR_927469.2 linkn.811C>T non_coding_transcript_exon_variant Exon 4 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF727ENST00000456806.3 linkc.623C>T p.Ala208Val missense_variant Exon 4 of 4 4 NM_001159522.3 ENSP00000485448.1 A8MUV8
ENSG00000285544ENST00000647787.1 linkn.197-17841C>T intron_variant Intron 1 of 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.623C>T (p.A208V) alteration is located in exon 4 (coding exon 4) of the ZNF727 gene. This alteration results from a C to T substitution at nucleotide position 623, causing the alanine (A) at amino acid position 208 to be replaced by a valine (V). 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
0.13
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
4.2
DANN
Benign
0.74
DEOGEN2
Benign
0.041
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.00023
N
LIST_S2
Benign
0.13
T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.084
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.24
T
Sift4G
Benign
0.13
T
Polyphen
0.73
P
Vest4
0.096
MutPred
0.54
Loss of ubiquitination at K207 (P = 0.0648);
MVP
0.014
ClinPred
0.14
T
GERP RS
-0.11
Varity_R
0.021
gMVP
0.0080

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: rs1352940568; hg19: chr7-63538050; API