rs375984

Variant names:

• chr6-29676725-C-T
• rs375984
• NM_001109809.5:c.123+156G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-29676725-C-T
• chr6-29676725-C-G

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.123+156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,852 control chromosomes in the GnomAD database, including 3,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (3843 hom., cov: 32)
• Consequence: ZFP57 NM_001109809.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.908
• Publications: 47 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp
• transient neonatal diabetes mellitus

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-29676725-C-T is Benign according to our data. Variant chr6-29676725-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271856.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.

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.123+156G>A		intron	N/A	NP_001103279.2	Q9NU63-3
	ZFP57	NM_001366333.2		c.-93-666G>A		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.123+156G>A		intron	N/A	ENSP00000366080.2	Q9NU63-3
	ZFP57	ENST00000488757.6	TSL:1	c.-93-666G>A		intron	N/A	ENSP00000418259.2	A0A7I2S1M6
	ZFP57	ENST00000931172.1		c.123+156G>A		intron	N/A	ENSP00000601231.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33498 AN: 151734 Hom.: 3829 Cov.: 32

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: 0.319

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.221 AC: 33533 AN: 151852 Hom.: 3843 Cov.: 32 AF XY: 0.218 AC XY: 16176 AN XY: 74218

African (AFR) AF: 0.206 AC: 8537 AN: 41418

American (AMR) AF: 0.238 AC: 3630 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1686 AN: 5146

South Asian (SAS) AF: 0.317 AC: 1521 AN: 4804

European-Finnish (FIN) AF: 0.127 AC: 1340 AN: 10584

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

European-Non Finnish (NFE) AF: 0.227 AC: 15415 AN: 67876

Other (OTH) AF: 0.230 AC: 484 AN: 2106

Alfa AF: 0.225 Hom.: 10814

Bravo AF: 0.224

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.73
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs375984;

hg19: chr6-29644502;

COSMIC: COSV65305583;

COSMIC: COSV65305583;