chr6-29677801-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109809.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	NM_001109809.5	MANE Select	c.-363-435G>T		intron	N/A	NP_001103279.2	Q9NU63-3
	ZFP57	NM_001366333.2		c.-93-1742G>T		intron	N/A	NP_001353262.1	A0A7I2S1M6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	ENST00000376883.2	TSL:5 MANE Select	c.-363-435G>T		intron	N/A	ENSP00000366080.2	Q9NU63-3
	ZFP57	ENST00000488757.6	TSL:1	c.-93-1742G>T		intron	N/A	ENSP00000418259.2	A0A7I2S1M6
	ZFP57	ENST00000931172.1		c.-798G>T		5_prime_UTR	Exon 1 of 4	ENSP00000601231.1

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

African (AFR) AF: 0.163 AC: 5697 AN: 34874

American (AMR) AF: 0.0544 AC: 617 AN: 11340

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 97 AN: 2854

East Asian (EAS) AF: 0.00489 AC: 14 AN: 2862

South Asian (SAS) AF: 0.00964 AC: 28 AN: 2904

European-Finnish (FIN) AF: 0.00312 AC: 27 AN: 8642

Middle Eastern (MID) AF: 0.0631 AC: 13 AN: 206

European-Non Finnish (NFE) AF: 0.0281 AC: 1404 AN: 50042

Other (OTH) AF: 0.0772 AC: 127 AN: 1646

Alfa AF: 0.0345 Hom.: 421

Bravo AF: 0.0608

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.72
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs387603; hg19: chr6-29645578;