rs9257940

Variant names:

• chr6-29674732-A-G
• rs9257940
• NM_001109809.5:c.352+654T>C

Variant summary

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

The NM_001109809.5(ZFP57):​c.352+654T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 152,252 control chromosomes in the GnomAD database, including 207 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 0.046 (207 hom., cov: 31)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.352+654T>C		intron_variant	Intron 4 of 4	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.136+654T>C		intron_variant	Intron 3 of 3		NP_001353262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2	c.352+654T>C		intron_variant	Intron 4 of 4	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.136+654T>C		intron_variant	Intron 3 of 3	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6991 AN: 152134 Hom.: 207 Cov.: 31

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0325

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0972

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0459 AC: 6988 AN: 152252 Hom.: 207 Cov.: 31 AF XY: 0.0461 AC XY: 3429 AN XY: 74454

African (AFR) AF: 0.0558 AC: 2320 AN: 41548

American (AMR) AF: 0.0324 AC: 496 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3472

East Asian (EAS) AF: 0.120 AC: 623 AN: 5182

South Asian (SAS) AF: 0.0973 AC: 470 AN: 4830

European-Finnish (FIN) AF: 0.0308 AC: 327 AN: 10602

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2410 AN: 68000

Other (OTH) AF: 0.0483 AC: 102 AN: 2112

Alfa AF: 0.0404 Hom.: 227

Bravo AF: 0.0458

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.72
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9257940; hg19: chr6-29642509;