rs3129063

chr6-29677836-C-Achr6-29677836-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001109809.5(ZFP57):c.-363-470G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 151,814 control chromosomes in the GnomAD database, including 2,553 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 0.17 (2553 hom., cov: 32)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP57	NM_001109809.5	c.-363-470G>T		intron_variant		ENST00000376883.2
ZFP57	NM_001366333.2	c.-93-1777G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP57	ENST00000376883.2	c.-363-470G>T		intron_variant		5	NM_001109809.5	P1
ZFP57	ENST00000488757.6	c.-93-1777G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25328 AN: 151696 Hom.: 2542 Cov.: 32

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.167 AC: 25353 AN: 151814 Hom.: 2553 Cov.: 32 AF XY: 0.166 AC XY: 12338 AN XY: 74186

Gnomad4 AFR AF: 0.0673

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.168

Alfa AF: 0.192 Hom.: 1117

Bravo AF: 0.163

Asia WGS AF: 0.382 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.28
Dann	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3129063; hg19: chr6-29645613;