Genetic Variant ZFP57:p.Arg517Thr (chr6-29672561-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001109809.5(ZFP57):c.1550G>C(p.Arg517Thr) 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. 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)

Consequence

ZFP57
NM_001109809.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

Publications

0 publications found

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]

ZFP57 links:

MOG (HGNC:7197): (myelin oligodendrocyte glycoprotein) The product of this gene is a membrane protein expressed on the oligodendrocyte cell surface and the outermost surface of myelin sheaths. Due to this localization, it is a primary target antigen involved in immune-mediated demyelination. This protein may be involved in completion and maintenance of the myelin sheath and in cell-cell communication. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MOG Gene-Disease associations (from GenCC):

narcolepsy 7
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MOG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07618037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109809.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP57	NM_001109809.5	MANE Select	c.1550G>C	p.Arg517Thr	missense	Exon 5 of 5	NP_001103279.2	Q9NU63-3
ZFP57	NM_001366333.2		c.1334G>C	p.Arg445Thr	missense	Exon 4 of 4	NP_001353262.1	A0A7I2S1M6
MOG	NM_206809.4	MANE Select	c.*1376C>G		downstream_gene	N/A	NP_996532.2	Q16653-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP57	ENST00000376883.2	TSL:5 MANE Select	c.1550G>C	p.Arg517Thr	missense	Exon 5 of 5	ENSP00000366080.2	Q9NU63-3
ZFP57	ENST00000488757.6	TSL:1	c.1334G>C	p.Arg445Thr	missense	Exon 4 of 4	ENSP00000418259.2	A0A7I2S1M6
ZFP57	ENST00000931172.1		c.1550G>C	p.Arg517Thr	missense	Exon 4 of 4	ENSP00000601231.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.78

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.055

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.52

M_CAP

Benign

0.0028

MetaRNN

Benign

0.076

MetaSVM

Benign

-0.93

PhyloP100

-1.2

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.71

REVEL

Benign

0.032

Sift

Benign

0.22

Sift4G

Benign

0.58

Polyphen

0.0010

Vest4

0.11

MutPred

0.48

Gain of loop (P = 0.0097)

MVP

0.17

MPC

0.62

ClinPred

0.23

GERP RS

0.56

Varity_R

0.054

gMVP

0.23

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over