16-31062207-A-T

Variant summary

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

The NM_024706.5(ZNF668):c.721T>A(p.Cys241Ser) 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. 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: 0.982

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41849953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF668	NM_024706.5	c.721T>A	p.Cys241Ser	missense_variant	3/3	ENST00000300849.5
ZNF668	NM_001172669.2	c.790T>A	p.Cys264Ser	missense_variant	4/4
ZNF668	NM_001172668.2	c.721T>A	p.Cys241Ser	missense_variant	3/3
ZNF668	NM_001172670.2	c.721T>A	p.Cys241Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF668	ENST00000300849.5	c.721T>A	p.Cys241Ser	missense_variant	3/3	1	NM_024706.5	P1
	ENST00000622229.1	n.2784A>T		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

Jul 14, 2021

The c.790T>A (p.C264S) alteration is located in exon 4 (coding exon 3) of the ZNF668 gene. This alteration results from a T to A substitution at nucleotide position 790, causing the cysteine (C) at amino acid position 264 to be replaced by a serine (S). 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	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Uncertain	25
Dann	Uncertain	0.98
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.51	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.42	T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.37	N;N;N;N;N;N
REVEL	Benign	0.29
Sift	Benign	0.14	T;T;T;T;T;T
Sift4G	Benign	0.60	T;T;T;T;T;T
Vest4		0.61
MutPred		0.27		Gain of phosphorylation at C241 (P = 0.0396);.;Gain of phosphorylation at C241 (P = 0.0396);Gain of phosphorylation at C241 (P = 0.0396);Gain of phosphorylation at C241 (P = 0.0396);.;
MVP		0.34
MPC		2.0
ClinPred		0.81	D
GERP RS		5.0
gMVP		0.54

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: chr16-31073528;