rs587780517

Positions:

• chr6-29673328-G-T
• chrNT_113891.3-1159801-G-T
• chrNT_167245.2-938874-G-T
• chrNT_167246.2-938442-G-T
• chrNT_167247.2-938702-G-T
• chrNT_167248.2-938829-G-T
• chrNT_167249.2-982360-G-T
• chr6-29673328-G-A
• chrNT_113891.3-1159801-G-A
• chrNT_167245.2-938874-G-A
• chrNT_167246.2-938442-G-A
• chrNT_167247.2-938702-G-A
• chrNT_167248.2-938829-G-A
• chrNT_167249.2-982360-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_001109809.5(ZFP57):​c.783C>A​(p.Cys261*) variant causes a stop gained change involving the alteration of a non-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). Synonymous variant affecting the same amino acid position (i.e. C261C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP57 NM_001109809.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.78

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.514 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-29673328-G-T is Pathogenic according to our data. Variant chr6-29673328-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 715.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.783C>A	p.Cys261*	stop_gained	5/5	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.567C>A	p.Cys189*	stop_gained	4/4		NP_001353262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2	c.783C>A	p.Cys261*	stop_gained	5/5	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.567C>A	p.Cys189*	stop_gained	4/4	1		ENSP00000418259.2

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

Submissions by phenotype

Diabetes mellitus, transient neonatal, 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Benign	-0.0034
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.73	D
Vest4		0.65
GERP RS		-1.4

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

Other links and lift over

dbSNP: rs61730328; hg19: chr6-29641105;