6-29676725-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001109809.5(ZFP57):c.123+156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,852 control chromosomes in the GnomAD database, including 3,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (3843 hom., cov: 32)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.908

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-29676725-C-T is Benign according to our data. Variant chr6-29676725-C-T is described in ClinVar as [Benign]. Clinvar id is 1271856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP57	NM_001109809.5	c.123+156G>A		intron_variant		ENST00000376883.2
ZFP57	NM_001366333.2	c.-93-666G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP57	ENST00000376883.2	c.123+156G>A		intron_variant		5	NM_001109809.5	P1
ZFP57	ENST00000488757.6	c.-93-666G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33498 AN: 151734 Hom.: 3829 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.221 AC: 33533 AN: 151852 Hom.: 3843 Cov.: 32 AF XY: 0.218 AC XY: 16176 AN XY: 74218

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.230

Alfa AF: 0.203 Hom.: 2703

Bravo AF: 0.224

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.20
Dann	Benign	0.73

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: rs375984; hg19: chr6-29644502; COSMIC: COSV65305583; COSMIC: COSV65305583;