6-29672829-C-A

Variant names:

• chr6-29672829-C-A
• rs758763239
• NM_001109809.5:c.1282G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V428I) has been classified as Uncertain significance.

• 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
• Publications: 0 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]

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]

MOG Gene-Disease associations (from GenCC):

• narcolepsy 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	NM_001109809.5	MANE Select	c.1282G>T	p.Val428Phe	missense	Exon 5 of 5	NP_001103279.2	Q9NU63-3
	ZFP57	NM_001366333.2		c.1066G>T	p.Val356Phe	missense	Exon 4 of 4	NP_001353262.1	A0A7I2S1M6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	ENST00000376883.2	TSL:5 MANE Select	c.1282G>T	p.Val428Phe	missense	Exon 5 of 5	ENSP00000366080.2	Q9NU63-3
	ZFP57	ENST00000488757.6	TSL:1	c.1066G>T	p.Val356Phe	missense	Exon 4 of 4	ENSP00000418259.2	A0A7I2S1M6
	ZFP57	ENST00000931172.1		c.1282G>T	p.Val428Phe	missense	Exon 4 of 4	ENSP00000601231.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.96	T
PhyloP100		-1.4
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.41	T
Polyphen		0.40	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
Mutation Taster		=96/4	polymorphism

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: rs758763239; hg19: chr6-29640606;