rs9257940

Positions:

• chr6-29674732-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.352+654T>C		intron_variant		ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.136+654T>C		intron_variant			NP_001353262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2	c.352+654T>C		intron_variant		5	NM_001109809.5	ENSP00000366080	P1
ZFP57	ENST00000488757.6	c.136+654T>C		intron_variant		1		ENSP00000418259

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

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.0324

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0973

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0483

Alfa AF: 0.0399 Hom.: 160

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9257940; hg19: chr6-29642509;