6-29672561-C-G

Variant names:

• chr6-29672561-C-G
• NM_001109809.5:c.1550G>C

Variant summary

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

The NM_001109809.5(ZFP57):​c.1550G>C​(p.Arg517Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP57 NM_001109809.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.23

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]

MOG (HGNC:7197): (myelin oligodendrocyte glycoprotein) The product of this gene is a membrane protein expressed on the oligodendrocyte cell surface and the outermost surface of myelin sheaths. Due to this localization, it is a primary target antigen involved in immune-mediated demyelination. This protein may be involved in completion and maintenance of the myelin sheath and in cell-cell communication. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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=0.07618037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.1550G>C	p.Arg517Thr	missense_variant	Exon 5 of 5	ENST00000376883.2	NP_001103279.2
MOG	NM_206809.4	c.*1376C>G		downstream_gene_variant		ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2	c.1550G>C	p.Arg517Thr	missense_variant	Exon 5 of 5	5	NM_001109809.5	ENSP00000366080.2
MOG	ENST00000376917.8	c.*1376C>G		downstream_gene_variant		1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Mar 23, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1550G>C (p.R517T) alteration is located in exon 4 (coding exon 4) of the ZFP57 gene. This alteration results from a G to C substitution at nucleotide position 1550, causing the arginine (R) at amino acid position 517 to be replaced by a threonine (T). 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	Benign	0.16
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.78
DANN	Benign	0.62
DEOGEN2	Benign	0.055	.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.52	T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.71	N;N;.
REVEL	Benign	0.032
Sift	Benign	0.22	T;T;.
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.11
MutPred		0.48		Gain of loop (P = 0.0097);.;.;
MVP		0.17
MPC		0.62
ClinPred		0.23	T
GERP RS		0.56
Varity_R		0.054
gMVP		0.23

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: chr6-29640338;