NM_001109809.5:c.-363-491G>A

Variant names:

• chr6-29677857-C-T
• rs387642
• NM_001109809.5:c.-363-491G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001109809.5(ZFP57):​c.-363-491G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,816 control chromosomes in the GnomAD database, including 3,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3823 hom., cov: 32)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 29 publications found

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 Gene-Disease associations (from GenCC):

• diabetes mellitus, transient neonatal, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• transient neonatal diabetes mellitus

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	NM_001109809.5	MANE Select	c.-363-491G>A		intron	N/A	NP_001103279.2
	ZFP57	NM_001366333.2		c.-93-1798G>A		intron	N/A	NP_001353262.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	ENST00000376883.2	TSL:5 MANE Select	c.-363-491G>A		intron	N/A	ENSP00000366080.2
	ZFP57	ENST00000488757.6	TSL:1	c.-93-1798G>A		intron	N/A	ENSP00000418259.2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33436 AN: 151698 Hom.: 3809 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.220 AC: 33471 AN: 151816 Hom.: 3823 Cov.: 32 AF XY: 0.218 AC XY: 16142 AN XY: 74176

African (AFR) AF: 0.206 AC: 8521 AN: 41370

American (AMR) AF: 0.237 AC: 3616 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1683 AN: 5152

South Asian (SAS) AF: 0.316 AC: 1517 AN: 4804

European-Finnish (FIN) AF: 0.126 AC: 1324 AN: 10540

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15408 AN: 67930

Other (OTH) AF: 0.230 AC: 485 AN: 2110

Alfa AF: 0.217 Hom.: 6140

Bravo AF: 0.224

Asia WGS AF: 0.398 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.32
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs387642; hg19: chr6-29645634;