rs2747430

Variant names:

• chr6-29680729-G-A
• rs2747430
• NM_001109809.5:c.-364+333C>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.-364+333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,060 control chromosomes in the GnomAD database, including 6,871 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 0.29 (6871 hom., cov: 31)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 37 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 = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.-364+333C>T		intron_variant	Intron 1 of 4	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.-94+333C>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.-364+333C>T		intron_variant	Intron 1 of 4	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.-94+333C>T		intron_variant	Intron 1 of 3	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44516 AN: 151942 Hom.: 6854 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.293 AC: 44560 AN: 152060 Hom.: 6871 Cov.: 31 AF XY: 0.292 AC XY: 21678 AN XY: 74326

African (AFR) AF: 0.244 AC: 10136 AN: 41492

American (AMR) AF: 0.316 AC: 4827 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3470

East Asian (EAS) AF: 0.499 AC: 2560 AN: 5126

South Asian (SAS) AF: 0.469 AC: 2259 AN: 4818

European-Finnish (FIN) AF: 0.179 AC: 1891 AN: 10586

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21036 AN: 67962

Other (OTH) AF: 0.296 AC: 626 AN: 2114

Alfa AF: 0.302 Hom.: 11544

Bravo AF: 0.298

Asia WGS AF: 0.497 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.75
PhyloP100		-1.1
PromoterAI		0.064	Neutral
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: rs2747430; hg19: chr6-29648506;