3-179333424-G-C

Variant names:

• chr3-179333424-G-C
• NM_001303426.2:c.460G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001303426.2(ZNF639):​c.460G>C​(p.Glu154Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF639 NM_001303426.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.52

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30747682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF639	NM_001303426.2	c.460G>C	p.Glu154Gln	missense_variant	Exon 6 of 6	ENST00000496856.6	NP_001290355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF639	ENST00000496856.6	c.460G>C	p.Glu154Gln	missense_variant	Exon 6 of 6	1	NM_001303426.2	ENSP00000417740.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.460G>C (p.E154Q) alteration is located in exon 7 (coding exon 4) of the ZNF639 gene. This alteration results from a G to C substitution at nucleotide position 460, causing the glutamic acid (E) at amino acid position 154 to be replaced by a glutamine (Q). 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	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T;T;T;T;T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.82	.;T;.;T;.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.31	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;L;.;L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.85	N;D;N;N;N;.
REVEL	Benign	0.24
Sift	Benign	0.20	T;D;T;D;T;.
Sift4G	Benign	0.12	T;T;T;T;T;T
Polyphen		0.99	D;.;D;.;D;D
Vest4		0.32
MutPred		0.23		Gain of glycosylation at Y151 (P = 0.0089);Gain of glycosylation at Y151 (P = 0.0089);Gain of glycosylation at Y151 (P = 0.0089);Gain of glycosylation at Y151 (P = 0.0089);Gain of glycosylation at Y151 (P = 0.0089);Gain of glycosylation at Y151 (P = 0.0089);
MVP		0.41
MPC		0.65
ClinPred		0.73	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.36

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: chr3-179051212;