NM_001109809.5:c.1282G>T

Variant names:

• chr6-29672829-C-A
• NM_001109809.5:c.1282G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001109809.5(ZFP57):​c.1282G>T​(p.Val428Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZFP57 NM_001109809.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09840083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.1282G>T	p.Val428Phe	missense_variant	Exon 5 of 5	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.1066G>T	p.Val356Phe	missense_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.1282G>T	p.Val428Phe	missense_variant	Exon 5 of 5	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.1066G>T	p.Val356Phe	missense_variant	Exon 4 of 4	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460770 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.55	T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D;D;.
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D;D;.
Sift4G	Benign	0.41	T;T;T
Polyphen		0.40	B;B;.
Vest4		0.23
MutPred		0.25		Loss of MoRF binding (P = 0.1006);.;.;
MVP		0.13
MPC		1.3
ClinPred		0.56	D
GERP RS		-3.0
Varity_R		0.056
gMVP		0.31

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-29640606;