6-29677836-C-A

Variant names:

• chr6-29677836-C-A
• rs3129063
• NM_001109809.5:c.-363-470G>T

Variant summary

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

The NM_001109809.5(ZFP57):​c.-363-470G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 151,814 control chromosomes in the GnomAD database, including 2,553 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 0.17 (2553 hom., cov: 32)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863
• Publications: 27 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.-363-470G>T		intron_variant	Intron 1 of 4	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.-93-1777G>T		intron_variant	Intron 1 of 3		NP_001353262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2	c.-363-470G>T		intron_variant	Intron 1 of 4	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.-93-1777G>T		intron_variant	Intron 1 of 3	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25328 AN: 151696 Hom.: 2542 Cov.: 32

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.167 AC: 25353 AN: 151814 Hom.: 2553 Cov.: 32 AF XY: 0.166 AC XY: 12338 AN XY: 74186

African (AFR) AF: 0.0673 AC: 2783 AN: 41380

American (AMR) AF: 0.196 AC: 2980 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1660 AN: 5140

South Asian (SAS) AF: 0.309 AC: 1484 AN: 4796

European-Finnish (FIN) AF: 0.122 AC: 1290 AN: 10552

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13998 AN: 67934

Other (OTH) AF: 0.168 AC: 354 AN: 2108

Alfa AF: 0.177 Hom.: 2012

Bravo AF: 0.163

Asia WGS AF: 0.382 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.36
PhyloP100		-0.86
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: rs3129063; hg19: chr6-29645613;