chr6-29672739-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_001109809.5(ZFP57):​c.1372C>G​(p.His458Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

ZFP57
NM_001109809.5 missense

Scores

8
6
4

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.21
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 Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.978
PP5
Variant 6-29672739-G-C is Pathogenic according to our data. Variant chr6-29672739-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 718.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZFP57NM_001109809.5 linkuse as main transcriptc.1372C>G p.His458Asp missense_variant 5/5 ENST00000376883.2
ZFP57NM_001366333.2 linkuse as main transcriptc.1156C>G p.His386Asp missense_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZFP57ENST00000376883.2 linkuse as main transcriptc.1372C>G p.His458Asp missense_variant 5/55 NM_001109809.5 P1Q9NU63-3
ZFP57ENST00000488757.6 linkuse as main transcriptc.1156C>G p.His386Asp missense_variant 4/41

Frequencies

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

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Diabetes mellitus, transient neonatal, 1 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMAug 01, 2008- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.64
.;.;D
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.69
T;T;T
M_CAP
Benign
0.047
D
MetaRNN
Pathogenic
0.98
D;D;D
MetaSVM
Uncertain
-0.24
T
MutationTaster
Benign
0.91
A;A;A
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-8.9
D;D;.
REVEL
Uncertain
0.35
Sift
Pathogenic
0.0
D;D;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.95
MutPred
0.80
Gain of ubiquitination at K463 (P = 0.0546);.;.;
MVP
0.61
MPC
1.5
ClinPred
1.0
D
GERP RS
4.5
Varity_R
0.22
gMVP
0.76

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: rs79020217; hg19: chr6-29640516; API