6-29679865-T-C

Variant names:

• chr6-29679865-T-C
• rs448489
• NM_001109809.5:c.-364+1197A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001109809.5(ZFP57):​c.-364+1197A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 150,916 control chromosomes in the GnomAD database, including 3,855 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 0.22 (3855 hom., cov: 32)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498
• Publications: 17 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.-364+1197A>G		intron_variant	Intron 1 of 4	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.-94+1197A>G		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.-364+1197A>G		intron_variant	Intron 1 of 4	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.-94+1197A>G		intron_variant	Intron 1 of 3	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33527 AN: 150800 Hom.: 3841 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.222 AC: 33562 AN: 150916 Hom.: 3855 Cov.: 32 AF XY: 0.220 AC XY: 16190 AN XY: 73656

African (AFR) AF: 0.208 AC: 8539 AN: 40988

American (AMR) AF: 0.240 AC: 3636 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3464

East Asian (EAS) AF: 0.330 AC: 1695 AN: 5134

South Asian (SAS) AF: 0.318 AC: 1518 AN: 4780

European-Finnish (FIN) AF: 0.129 AC: 1327 AN: 10278

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

European-Non Finnish (NFE) AF: 0.228 AC: 15442 AN: 67830

Other (OTH) AF: 0.231 AC: 484 AN: 2092

Alfa AF: 0.105 Hom.: 179

Bravo AF: 0.224

Asia WGS AF: 0.397 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.6
DANN	Benign	0.14
PhyloP100		-0.50
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: rs448489; hg19: chr6-29647642;