6-29672748-G-A

Variant names:

• chr6-29672748-G-A
• rs1378380148
• NM_001109809.5:c.1363C>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.1363C>T​(p.Leu455Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ZFP57 NM_001109809.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31

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=0.23407221).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.1363C>T	p.Leu455Phe	missense_variant	Exon 5 of 5	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2	c.1147C>T	p.Leu383Phe	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.1363C>T	p.Leu455Phe	missense_variant	Exon 5 of 5	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6	c.1147C>T	p.Leu383Phe	missense_variant	Exon 4 of 4	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1363C>T (p.L455F) alteration is located in exon 4 (coding exon 4) of the ZFP57 gene. This alteration results from a C to T substitution at nucleotide position 1363, causing the leucine (L) at amino acid position 455 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	.;.;T
Eigen	Benign	0.0010
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.5	D;D;N
REVEL	Benign	0.19
Sift	Benign	0.037	D;D;T
Sift4G	Uncertain	0.011	D;D;T
Polyphen		1.0	D;D;.
Vest4		0.44
MVP		0.69
MPC		0.57
ClinPred		0.68	D
GERP RS		2.7
Varity_R		0.031
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs1378380148; hg19: chr6-29640525;