rs378596

Positions:

• chr6-29675510-A-C

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.251-23T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,599,582 control chromosomes in the GnomAD database, including 1,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (435 hom., cov: 31)
  • Exomes 𝑓: 0.021 (626 hom.)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.160

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=-0.87).
• BP6: Variant 6-29675510-A-C is Benign according to our data. Variant chr6-29675510-A-C is described in ClinVar as [Benign]. Clinvar id is 1242039.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP57	NM_001109809.5	c.251-23T>G		intron_variant		ENST00000376883.2
ZFP57	NM_001366333.2	c.35-23T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP57	ENST00000376883.2	c.251-23T>G		intron_variant		5	NM_001109809.5	P1
ZFP57	ENST00000488757.6	c.35-23T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8053 AN: 152038 Hom.: 433 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0612

GnomAD3 exomes AF: 0.0241 AC: 6018 AN: 249398 Hom.: 217 AF XY: 0.0218 AC XY: 2946 AN XY: 135292

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.0234

Gnomad ASJ exome AF: 0.0266

Gnomad EAS exome AF: 0.00273

Gnomad SAS exome AF: 0.00791

Gnomad FIN exome AF: 0.00218

Gnomad NFE exome AF: 0.0198

Gnomad OTH exome AF: 0.0282

GnomAD4 exome AF: 0.0205 AC: 29736 AN: 1447426 Hom.: 626 Cov.: 28 AF XY: 0.0198 AC XY: 14251 AN XY: 721140

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0263

Gnomad4 ASJ exome AF: 0.0250

Gnomad4 EAS exome AF: 0.00169

Gnomad4 SAS exome AF: 0.00801

Gnomad4 FIN exome AF: 0.00285

Gnomad4 NFE exome AF: 0.0187

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0530 AC: 8062 AN: 152156 Hom.: 435 Cov.: 31 AF XY: 0.0506 AC XY: 3769 AN XY: 74414

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.0207

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0270 Hom.: 143

Bravo AF: 0.0608

Asia WGS AF: 0.0160 AC: 55 AN: 3478

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

May 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs378596; hg19: chr6-29643287;