rs378596

Variant names:

• chr6-29675510-A-C
• rs378596
• NM_001109809.5:c.251-23T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-29675510-A-C
• chr6-29675510-A-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 VariationId 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 rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.251-23T>G		intron_variant	Intron 3 of 4	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.35-23T>G		intron_variant	Intron 2 of 3		NP_001353262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2	c.251-23T>G		intron_variant	Intron 3 of 4	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.35-23T>G		intron_variant	Intron 2 of 3	1		ENSP00000418259.2

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

GnomAD2 exomes AF: 0.0241 AC: 6018 AN: 249398 AF XY: 0.0218

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 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

African (AFR) AF: 0.142 AC: 4704 AN: 33166

American (AMR) AF: 0.0263 AC: 1174 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0250 AC: 651 AN: 26038

East Asian (EAS) AF: 0.00169 AC: 67 AN: 39614

South Asian (SAS) AF: 0.00801 AC: 689 AN: 85986

European-Finnish (FIN) AF: 0.00285 AC: 152 AN: 53414

Middle Eastern (MID) AF: 0.0450 AC: 259 AN: 5752

European-Non Finnish (NFE) AF: 0.0187 AC: 20569 AN: 1098812

Other (OTH) AF: 0.0245 AC: 1471 AN: 59936

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

African (AFR) AF: 0.138 AC: 5724 AN: 41480

American (AMR) AF: 0.0407 AC: 621 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5178

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4824

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10610

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0207 AC: 1406 AN: 68014

Other (OTH) AF: 0.0601 AC: 127 AN: 2114

Alfa AF: 0.0348 Hom.: 536

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

May 21, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs378596; hg19: chr6-29643287;