NM_001109809.5:c.1529C>T

Variant names:

• chr6-29672582-G-A
• rs773321909
• NM_001109809.5:c.1529C>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.1529C>T​(p.Thr510Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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: 0.0000014 (0 hom.)
• Consequence: ZFP57 NM_001109809.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

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=0.087210834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5	c.1529C>T	p.Thr510Ile	missense_variant	Exon 5 of 5	ENST00000376883.2	NP_001103279.2
MOG	NM_206809.4	c.*1397G>A		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.1529C>T	p.Thr510Ile	missense_variant	Exon 5 of 5	5	NM_001109809.5	ENSP00000366080.2
MOG	ENST00000376917.8	c.*1397G>A		downstream_gene_variant		1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460502 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726534

Gnomad4 AFR exome AF: 0.0000299

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: 0.0000191

Gnomad4 NFE exome AF: 0.00

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	Benign	0.17
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.52
DANN	Benign	0.33
DEOGEN2	Benign	0.30	.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.45	T;T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.1	N;N;.
REVEL	Benign	0.028
Sift	Benign	0.050	D;D;.
Sift4G	Benign	0.065	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.18
MutPred		0.30		Loss of phosphorylation at T510 (P = 0.0013);.;.;
MVP		0.18
MPC		0.45
ClinPred		0.16	T
GERP RS		-1.9
Varity_R		0.031
gMVP		0.060

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: rs773321909; hg19: chr6-29640359;