chr6-29672858-C-A

Variant summary

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

The NM_001109809.5(ZFP57):​c.1253G>T​(p.Ser418Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZFP57
NM_001109809.5 missense

Scores

1
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.584
Variant links:
Genes affected
ZFP57 (HGNC:18791): (ZFP57 zinc finger protein) The protein encoded by this gene is a zinc finger protein containing a KRAB domain. Studies in mouse suggest that this protein may function as a transcriptional repressor. Mutations in this gene have been associated with transient neonatal diabetes mellitus type 1 (TNDM1).[provided by RefSeq, Sep 2009]

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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=0.23724422).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZFP57NM_001109809.5 linkuse as main transcriptc.1253G>T p.Ser418Ile missense_variant 5/5 ENST00000376883.2
ZFP57NM_001366333.2 linkuse as main transcriptc.1037G>T p.Ser346Ile missense_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZFP57ENST00000376883.2 linkuse as main transcriptc.1253G>T p.Ser418Ile missense_variant 5/55 NM_001109809.5 P1Q9NU63-3
ZFP57ENST00000488757.6 linkuse as main transcriptc.1037G>T p.Ser346Ile missense_variant 4/41

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeDec 07, 2023This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 418 of the ZFP57 protein (p.Ser418Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZFP57-related conditions. ClinVar contains an entry for this variant (Variation ID: 1976445). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
.;.;T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.24
T;T;T
MetaSVM
Benign
-0.94
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-4.0
D;D;.
REVEL
Benign
0.043
Sift
Uncertain
0.0030
D;D;.
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
0.46
P;P;.
Vest4
0.27
MutPred
0.68
Loss of disorder (P = 0.0012);.;.;
MVP
0.30
MPC
1.0
ClinPred
0.54
D
GERP RS
2.6
Varity_R
0.065
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-29640635; API