rs387603

Variant names:

• chr6-29677801-C-A
• rs387603
• NM_001109809.5:c.-363-435G>T

Variant summary

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

The NM_001109809.5(ZFP57):​c.-363-435G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 116,012 control chromosomes in the GnomAD database, including 428 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 0.069 (428 hom., cov: 31)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.-363-435G>T		intron_variant	Intron 1 of 4	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.-93-1742G>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.-363-435G>T		intron_variant	Intron 1 of 4	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.-93-1742G>T		intron_variant	Intron 1 of 3	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 8016 AN: 115936 Hom.: 426 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00156

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.00488

Gnomad SAS AF: 0.00999

Gnomad FIN AF: 0.00312

Gnomad MID AF: 0.0721

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.0692 AC: 8025 AN: 116012 Hom.: 428 Cov.: 31 AF XY: 0.0662 AC XY: 3744 AN XY: 56592

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0544

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.00489

Gnomad4 SAS AF: 0.00964

Gnomad4 FIN AF: 0.00312

Gnomad4 NFE AF: 0.0281

Gnomad4 OTH AF: 0.0772

Alfa AF: 0.0371 Hom.: 69

Bravo AF: 0.0608

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs387603; hg19: chr6-29645578;