rs2747431

Variant names:

• chr6-29680787-C-T
• rs2747431
• NM_001109809.5:c.-364+275G>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.-364+275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,030 control chromosomes in the GnomAD database, including 5,946 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 0.27 (5946 hom., cov: 31)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 24 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.-364+275G>A		intron_variant	Intron 1 of 4	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.-94+275G>A		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+275G>A		intron_variant	Intron 1 of 4	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.-94+275G>A		intron_variant	Intron 1 of 3	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41117 AN: 151912 Hom.: 5933 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.271 AC: 41152 AN: 152030 Hom.: 5946 Cov.: 31 AF XY: 0.270 AC XY: 20060 AN XY: 74298

African (AFR) AF: 0.218 AC: 9053 AN: 41484

American (AMR) AF: 0.280 AC: 4271 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2536 AN: 5140

South Asian (SAS) AF: 0.456 AC: 2198 AN: 4818

European-Finnish (FIN) AF: 0.164 AC: 1739 AN: 10584

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19556 AN: 67946

Other (OTH) AF: 0.276 AC: 585 AN: 2116

Alfa AF: 0.279 Hom.: 2422

Bravo AF: 0.271

Asia WGS AF: 0.487 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.79
PhyloP100		-1.9
PromoterAI		-0.025	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: rs2747431; hg19: chr6-29648564;