rs1555498115

chr16-31061919-T-C

Variant summary

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

The NM_024706.5(ZNF668):c.1009A>G(p.Lys337Glu) 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. 11/19 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: 0.928

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=0.13071823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF668	NM_024706.5	c.1009A>G	p.Lys337Glu	missense_variant	3/3	ENST00000300849.5
ZNF668	NM_001172669.2	c.1078A>G	p.Lys360Glu	missense_variant	4/4
ZNF668	NM_001172668.2	c.1009A>G	p.Lys337Glu	missense_variant	3/3
ZNF668	NM_001172670.2	c.1009A>G	p.Lys337Glu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF668	ENST00000300849.5	c.1009A>G	p.Lys337Glu	missense_variant	3/3	1	NM_024706.5	P1
	ENST00000622229.1	n.2496T>C		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 provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
Cadd	Benign	23
Dann	Benign	0.96
Eigen	Benign	-0.032
Eigen_PC	Benign	0.0022
FATHMM_MKL	Benign	0.62	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-0.66	T
MutationTaster	Benign	0.86	D;D;D;D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.63	N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.47	T;T;T;T;T;T
Sift4G	Benign	0.47	T;T;T;T;T;T
Vest4		0.20
MutPred		0.42		Loss of methylation at K337 (P = 0);.;Loss of methylation at K337 (P = 0);Loss of methylation at K337 (P = 0);Loss of methylation at K337 (P = 0);.;
MVP		0.50
MPC		1.2
ClinPred		0.45	T
GERP RS		4.5
gMVP		0.84

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

LitVar

Other links and lift over

dbSNP: rs1555498115; hg19: chr16-31073240;