3-179333719-C-G

Variant names:

• chr3-179333719-C-G
• rs145622829
• NM_001303426.2:c.755C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001303426.2(ZNF639):​c.755C>G​(p.Ala252Gly) 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. 15/22 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. A252V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF639 NM_001303426.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

Genes affected

ZNF639 (HGNC:30950): (zinc finger protein 639) This gene encodes a member of the Kruppel-like zinc finger family of proteins. Amplification and overexpression of this gene have been observed in esophageal squamous cell carcinoma. The encoded protein has been shown to bind DNA in a sequence-specific manner and may regulate HIV-1 gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

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=0.24526623).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303426.2. 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
	ZNF639	NM_001303426.2	MANE Select	c.755C>G	p.Ala252Gly	missense	Exon 6 of 6	NP_001290355.1	Q9UID6
	ZNF639	NM_001303425.2		c.755C>G	p.Ala252Gly	missense	Exon 7 of 7	NP_001290354.1	Q9UID6
	ZNF639	NM_001375800.1		c.755C>G	p.Ala252Gly	missense	Exon 7 of 7	NP_001362729.1	Q9UID6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF639	ENST00000496856.6	TSL:1 MANE Select	c.755C>G	p.Ala252Gly	missense	Exon 6 of 6	ENSP00000417740.1	Q9UID6
	ZNF639	ENST00000326361.7	TSL:1	c.755C>G	p.Ala252Gly	missense	Exon 7 of 7	ENSP00000325634.3	Q9UID6
	ZNF639	ENST00000621687.1	TSL:1	c.755C>G	p.Ala252Gly	missense	Exon 4 of 4	ENSP00000477626.1	Q9UID6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.12
Sift	Benign	0.18	T
Sift4G	Benign	0.37	T
Polyphen		0.47	P
Vest4		0.063
MutPred		0.50		Loss of stability (P = 0.0811)
MVP		0.58
MPC		0.21
ClinPred		0.37	T
GERP RS		4.9
Varity_R		0.082
gMVP		0.26
Mutation Taster		=90/10	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: rs145622829; hg19: chr3-179051507;