19-56442216-T-C

Position:

• chr19-56442216-T-C

Variant summary

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

The NM_001321356.2(ZNF667):​c.779A>G​(p.Lys260Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,613,880 control chromosomes in the GnomAD database, including 239,174 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.55 (23386 hom., cov: 33)
  • Exomes 𝑓: 0.54 (215788 hom.)
• Consequence: ZNF667 NM_001321356.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

Genes affected

ZNF667 (HGNC:28854): (zinc finger protein 667) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.660318E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF667	NM_001321356.2	c.779A>G	p.Lys260Arg	missense_variant	7/7	ENST00000504904.8	NP_001308285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF667	ENST00000504904.8	c.779A>G	p.Lys260Arg	missense_variant	7/7	2	NM_001321356.2	ENSP00000439402.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83311 AN: 151990 Hom.: 23359 Cov.: 33

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.525

GnomAD3 exomes AF: 0.575 AC: 144269 AN: 250930 Hom.: 42751 AF XY: 0.569 AC XY: 77116 AN XY: 135642

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.647

Gnomad ASJ exome AF: 0.440

Gnomad EAS exome AF: 0.882

Gnomad SAS exome AF: 0.603

Gnomad FIN exome AF: 0.607

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.542

GnomAD4 exome AF: 0.538 AC: 786974 AN: 1461774 Hom.: 215788 Cov.: 73 AF XY: 0.539 AC XY: 392024 AN XY: 727168

Gnomad4 AFR exome AF: 0.518

Gnomad4 AMR exome AF: 0.643

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.884

Gnomad4 SAS exome AF: 0.597

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.539

GnomAD4 genome AF: 0.548 AC: 83391 AN: 152106 Hom.: 23386 Cov.: 33 AF XY: 0.554 AC XY: 41216 AN XY: 74366

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.881

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.529

Alfa AF: 0.522 Hom.: 40799

Bravo AF: 0.546

TwinsUK AF: 0.520 AC: 1929

ALSPAC AF: 0.533 AC: 2056

ESP6500AA AF: 0.520 AC: 2289

ESP6500EA AF: 0.522 AC: 4490

ExAC AF: 0.570 AC: 69202

Asia WGS AF: 0.740 AC: 2569 AN: 3478

EpiCase AF: 0.506

EpiControl AF: 0.497

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.082	T;T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.57	.;T;T
MetaRNN	Benign	9.7e-7	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.5	N;N;.
REVEL	Benign	0.064
Sift	Benign	0.16	T;T;.
Sift4G	Uncertain	0.032	D;D;D
Polyphen		0.12	B;B;.
Vest4		0.055
MPC		0.091
ClinPred		0.0084	T
GERP RS		2.9
Varity_R		0.13
gMVP		0.023

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: rs3760849; hg19: chr19-56953585;