chr6-29681328-G-A

Variant names:

• chr6-29681328-G-A
• rs3131847
• NM_001109809.5:c.-630C>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.-630C>T 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 151,756 control chromosomes in the GnomAD database, including 9,830 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 (9830 hom., cov: 29)
• Consequence: ZFP57 NM_001109809.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.-630C>T		upstream_gene_variant		ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.-360C>T		upstream_gene_variant			NP_001353262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2	c.-630C>T		upstream_gene_variant		5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.-360C>T		upstream_gene_variant		1		ENSP00000418259.2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53173 AN: 151638 Hom.: 9819 Cov.: 29

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.427

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: 53221 AN: 151756 Hom.: 9830 Cov.: 29 AF XY: 0.349 AC XY: 25840 AN XY: 74130

African (AFR) AF: 0.419 AC: 17324 AN: 41340

American (AMR) AF: 0.422 AC: 6431 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1663 AN: 3466

East Asian (EAS) AF: 0.245 AC: 1263 AN: 5148

South Asian (SAS) AF: 0.358 AC: 1725 AN: 4812

European-Finnish (FIN) AF: 0.202 AC: 2129 AN: 10542

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21507 AN: 67896

Other (OTH) AF: 0.391 AC: 825 AN: 2108

Alfa AF: 0.341 Hom.: 5243

Bravo AF: 0.374

Asia WGS AF: 0.254 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.84
DANN	Benign	0.59
PhyloP100		-0.62
PromoterAI		0.011	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3131847; hg19: chr6-29649105;