rs2535238

Variant names:

• chr6-29677261-C-A
• rs2535238
• NM_001109809.5:c.-258G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-29677261-C-A
• chr6-29677261-C-G
• chr6-29677261-C-T

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.-258G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 551,838 control chromosomes in the GnomAD database, including 16,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3861 hom., cov: 33)
  • Exomes 𝑓: 0.24 (12139 hom.)
• Consequence: ZFP57 NM_001109809.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.159
• Publications: 58 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=-0.8).
• BP6: Variant 6-29677261-C-A is Benign according to our data. Variant chr6-29677261-C-A is described in ClinVar as Benign. ClinVar VariationId is 1251245.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 rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.-258G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001109809.5	c.-258G>T		5_prime_UTR_variant	Exon 2 of 5	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.-93-1202G>T		intron_variant	Intron 1 of 3		NP_001353262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2	c.-258G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000376883.2	c.-258G>T		5_prime_UTR_variant	Exon 2 of 5	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.-93-1202G>T		intron_variant	Intron 1 of 3	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33588 AN: 152106 Hom.: 3847 Cov.: 33

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: 0.318

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.238 AC: 94992 AN: 399614 Hom.: 12139 Cov.: 4 AF XY: 0.242 AC XY: 51233 AN XY: 212072

African (AFR) AF: 0.208 AC: 2377 AN: 11424

American (AMR) AF: 0.251 AC: 4220 AN: 16842

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 2217 AN: 12088

East Asian (EAS) AF: 0.345 AC: 8992 AN: 26092

South Asian (SAS) AF: 0.307 AC: 13652 AN: 44418

European-Finnish (FIN) AF: 0.139 AC: 3261 AN: 23424

Middle Eastern (MID) AF: 0.204 AC: 680 AN: 3328

European-Non Finnish (NFE) AF: 0.226 AC: 54094 AN: 238866

Other (OTH) AF: 0.238 AC: 5499 AN: 23132

GnomAD4 genome AF: 0.221 AC: 33623 AN: 152224 Hom.: 3861 Cov.: 33 AF XY: 0.218 AC XY: 16224 AN XY: 74414

African (AFR) AF: 0.206 AC: 8573 AN: 41530

American (AMR) AF: 0.238 AC: 3635 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3470

East Asian (EAS) AF: 0.328 AC: 1699 AN: 5182

South Asian (SAS) AF: 0.315 AC: 1520 AN: 4818

European-Finnish (FIN) AF: 0.126 AC: 1340 AN: 10614

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15450 AN: 68006

Other (OTH) AF: 0.229 AC: 485 AN: 2116

Alfa AF: 0.226 Hom.: 12182

Bravo AF: 0.225

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 13, 2018

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	-0.80
CADD	Benign	8.2
DANN	Benign	0.80
PhyloP100		0.16
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2535238; hg19: chr6-29645038;