6-29681279-C-T

Variant names:

• chr6-29681279-C-T
• rs3129054
• NM_001109809.5:c.-581G>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.-581G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,254 control chromosomes in the GnomAD database, including 9,823 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 0.35 (9823 hom., cov: 27)
• Consequence: ZFP57 NM_001109809.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.993
• Publications: 28 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 (AMR) allele frequency at 95% confidence interval = 0.414 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	NM_001109809.5	MANE Select	c.-581G>A		upstream_gene	N/A	NP_001103279.2	Q9NU63-3
	ZFP57	NM_001366333.2		c.-311G>A		upstream_gene	N/A	NP_001353262.1	A0A7I2S1M6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	ENST00000376883.2	TSL:5 MANE Select	c.-581G>A		upstream_gene	N/A	ENSP00000366080.2	Q9NU63-3
	ZFP57	ENST00000488757.6	TSL:1	c.-311G>A		upstream_gene	N/A	ENSP00000418259.2	A0A7I2S1M6

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53026 AN: 151138 Hom.: 9812 Cov.: 27

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.351 AC: 53074 AN: 151254 Hom.: 9823 Cov.: 27 AF XY: 0.349 AC XY: 25773 AN XY: 73852

African (AFR) AF: 0.419 AC: 17262 AN: 41170

American (AMR) AF: 0.422 AC: 6418 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1660 AN: 3464

East Asian (EAS) AF: 0.246 AC: 1261 AN: 5116

South Asian (SAS) AF: 0.358 AC: 1706 AN: 4764

European-Finnish (FIN) AF: 0.202 AC: 2106 AN: 10448

Middle Eastern (MID) AF: 0.441 AC: 128 AN: 290

European-Non Finnish (NFE) AF: 0.317 AC: 21490 AN: 67804

Other (OTH) AF: 0.391 AC: 821 AN: 2098

Alfa AF: 0.338 Hom.: 27295

Bravo AF: 0.374

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.79
DANN	Benign	0.68
PhyloP100		-0.99
PromoterAI		-0.033	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3129054; hg19: chr6-29649056;