rs587780516

Variant names:

• chr6-29673518-T-C
• rs9461544
• NM_001109809.5:c.593A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-29673518-T-C
• chrNT_113891.3-1159991-T-C
• chrNT_167245.2-939064-T-C
• chrNT_167246.2-938632-T-C
• chrNT_167247.2-938892-T-C
• chrNT_167248.2-939019-T-C
• chrNT_167249.2-982550-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001109809.5(ZFP57):​c.593A>G​(p.Asn198Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,613,052 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (101 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (82 hom.)
• Consequence: ZFP57 NM_001109809.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.993
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022326708).
• BP6: Variant 6-29673518-T-C is Benign according to our data. Variant chr6-29673518-T-C is described in ClinVar as Benign. ClinVar VariationId is 130771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0642 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	NM_001109809.5	MANE Select	c.593A>G	p.Asn198Ser	missense	Exon 5 of 5	NP_001103279.2
	ZFP57	NM_001366333.2		c.377A>G	p.Asn126Ser	missense	Exon 4 of 4	NP_001353262.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	ENST00000376883.2	TSL:5 MANE Select	c.593A>G	p.Asn198Ser	missense	Exon 5 of 5	ENSP00000366080.2
	ZFP57	ENST00000488757.6	TSL:1	c.377A>G	p.Asn126Ser	missense	Exon 4 of 4	ENSP00000418259.2

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2909 AN: 152168 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0144

GnomAD2 exomes AF: 0.00509 AC: 1246 AN: 244666 AF XY: 0.00412

Gnomad AFR exome AF: 0.0708

Gnomad AMR exome AF: 0.00462

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000109

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00222 AC: 3239 AN: 1460766 Hom.: 82 Cov.: 31 AF XY: 0.00196 AC XY: 1425 AN XY: 726698

African (AFR) AF: 0.0725 AC: 2426 AN: 33480

American (AMR) AF: 0.00568 AC: 254 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00204 AC: 176 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52310

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.0000890 AC: 99 AN: 1112004

Other (OTH) AF: 0.00432 AC: 261 AN: 60386

GnomAD4 genome AF: 0.0192 AC: 2920 AN: 152286 Hom.: 101 Cov.: 32 AF XY: 0.0193 AC XY: 1438 AN XY: 74462

African (AFR) AF: 0.0663 AC: 2753 AN: 41532

American (AMR) AF: 0.00791 AC: 121 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68024

Other (OTH) AF: 0.0142 AC: 30 AN: 2110

Alfa AF: 0.00796 Hom.: 77

Bravo AF: 0.0222

ESP6500AA AF: 0.0611 AC: 159

ESP6500EA AF: 0.000195 AC: 1

ExAC AF: 0.00576 AC: 672

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Diabetes mellitus, transient neonatal, 1 (2)
-	-	2	not provided (2)
-	-	1	Monogenic diabetes (1)
-	-	1	not specified (1)
-	-	1	ZFP57-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.019
DANN	Benign	0.38
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.99
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.013
Sift	Benign	0.77	T
Sift4G	Benign	0.70	T
Polyphen		0.11	B
Vest4		0.022
MVP		0.15
MPC		0.34
ClinPred		0.0022	T
GERP RS		-2.3
Varity_R		0.024
gMVP		0.027
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

Other links and lift over

dbSNP: rs9461544; hg19: chr6-29641295;