16-31061640-C-A

Variant summary

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

The NM_024706.5(ZNF668):c.1288G>T(p.Val430Leu) 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. 12/19 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: ZNF668 NM_024706.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.387

Genes affected

ZNF668 (HGNC:25821): (zinc finger protein 668) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

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=0.0821006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF668	NM_024706.5	c.1288G>T	p.Val430Leu	missense_variant	3/3	ENST00000300849.5
ZNF668	NM_001172669.2	c.1357G>T	p.Val453Leu	missense_variant	4/4
ZNF668	NM_001172668.2	c.1288G>T	p.Val430Leu	missense_variant	3/3
ZNF668	NM_001172670.2	c.1288G>T	p.Val430Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF668	ENST00000300849.5	c.1288G>T	p.Val430Leu	missense_variant	3/3	1	NM_024706.5	P1
	ENST00000622229.1	n.2217C>A		non_coding_transcript_exon_variant	2/2	2

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2023

The c.1357G>T (p.V453L) alteration is located in exon 4 (coding exon 3) of the ZNF668 gene. This alteration results from a G to T substitution at nucleotide position 1357, causing the valine (V) at amino acid position 453 to be replaced by a leucine (L). 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	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	17
Dann	Uncertain	0.98
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.27	N
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.082	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	N;N;N;N;N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.13	N;N;N;N;N;N
REVEL	Benign	0.073
Sift	Benign	0.32	T;T;T;T;T;T
Sift4G	Uncertain	0.027	D;D;D;D;D;D
Vest4		0.085
MutPred		0.52		Loss of catalytic residue at V430 (P = 0.0057);.;Loss of catalytic residue at V430 (P = 0.0057);Loss of catalytic residue at V430 (P = 0.0057);Loss of catalytic residue at V430 (P = 0.0057);.;
MVP		0.46
MPC		0.83
ClinPred		0.089	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr16-31072961;