rs8046978

chr16-31061588-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024706.5(ZNF668):c.1340C>T(p.Ala447Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,608,640 control chromosomes in the GnomAD database, including 37,883 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2520 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35363 hom.)
• Consequence: ZNF668 NM_024706.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032924712).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF668	NM_024706.5	c.1340C>T	p.Ala447Val	missense_variant	3/3	ENST00000300849.5
ZNF668	NM_001172669.2	c.1409C>T	p.Ala470Val	missense_variant	4/4
ZNF668	NM_001172668.2	c.1340C>T	p.Ala447Val	missense_variant	3/3
ZNF668	NM_001172670.2	c.1340C>T	p.Ala447Val	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF668	ENST00000300849.5	c.1340C>T	p.Ala447Val	missense_variant	3/3	1	NM_024706.5	P1
	ENST00000622229.1	n.2165G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24836 AN: 152066 Hom.: 2520 Cov.: 32

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.164

GnomAD3 exomes AF: 0.163 AC: 39496 AN: 242504 Hom.: 4008 AF XY: 0.167 AC XY: 22088 AN XY: 132388

Gnomad AFR exome AF: 0.0554

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.142

Gnomad EAS exome AF: 0.00223

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.179

GnomAD4 exome AF: 0.211 AC: 307466 AN: 1456456 Hom.: 35363 Cov.: 33 AF XY: 0.209 AC XY: 151810 AN XY: 724810

Gnomad4 AFR exome AF: 0.0533

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.00166

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.163 AC: 24839 AN: 152184 Hom.: 2520 Cov.: 32 AF XY: 0.161 AC XY: 12000 AN XY: 74380

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.162

Alfa AF: 0.198 Hom.: 1520

Bravo AF: 0.152

TwinsUK AF: 0.242 AC: 897

ALSPAC AF: 0.250 AC: 963

ESP6500AA AF: 0.0586 AC: 257

ESP6500EA AF: 0.228 AC: 1956

ExAC AF: 0.162 AC: 19537

Asia WGS AF: 0.0540 AC: 189 AN: 3478

EpiCase AF: 0.222

EpiControl AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	1.4
Dann	Benign	0.97
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
MetaRNN	Benign	0.0033	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.40	N;N;N;N;N;N
REVEL	Benign	0.035
Sift	Benign	0.33	T;T;T;T;T;T
Sift4G	Benign	0.55	T;T;T;T;T;T
Vest4		0.042
MPC		0.84
ClinPred		0.0052	T
GERP RS		-1.8
gMVP		0.26

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: rs8046978; hg19: chr16-31072909; COSMIC: COSV56211749; COSMIC: COSV56211749;