rs606231123

Variant names:

• chr6-29673205-AGCCTGGGT-A
• rs606231123
• NM_001109809.5:c.898_905delACCCAGGC

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PVS1_Strong PP5 BS2_Supporting

The NM_001109809.5(ZFP57):​c.898_905delACCCAGGC​(p.Thr300fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ZFP57 NM_001109809.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.00200

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 Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.443 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PP5: Variant 6-29673205-AGCCTGGGT-A is Pathogenic according to our data. Variant chr6-29673205-AGCCTGGGT-A is described in ClinVar as [Pathogenic]. Clinvar id is 721.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.898_905delACCCAGGC	p.Thr300fs	frameshift_variant	Exon 5 of 5	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.682_689delACCCAGGC	p.Thr228fs	frameshift_variant	Exon 4 of 4		NP_001353262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2	c.898_905delACCCAGGC	p.Thr300fs	frameshift_variant	Exon 5 of 5	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.682_689delACCCAGGC	p.Thr228fs	frameshift_variant	Exon 4 of 4	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244686 Hom.: 0 AF XY: 0.00000747 AC XY: 1 AN XY: 133908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000907

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460766 Hom.: 0 AF XY: 0.00000550 AC XY: 4 AN XY: 726702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Diabetes mellitus, transient neonatal, 1 Pathogenic:1

Aug 01, 2008

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs606231123; hg19: chr6-29640982;