chr19-56442216-T-C

Variant names:

• chr19-56442216-T-C
• rs3760849
• NM_001321356.2:c.779A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022103.4(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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (23386 hom., cov: 33)
  • Exomes 𝑓: 0.54 (215788 hom.)
• Consequence: ZNF667 NM_022103.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022103.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF667	NM_001321356.2	MANE Select	c.779A>G	p.Lys260Arg	missense	Exon 7 of 7	NP_001308285.1
	ZNF667	NM_022103.4		c.779A>G	p.Lys260Arg	missense	Exon 5 of 5	NP_071386.3
	ZNF667	NM_001321355.2		c.608A>G	p.Lys203Arg	missense	Exon 6 of 6	NP_001308284.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF667	ENST00000504904.8	TSL:2 MANE Select	c.779A>G	p.Lys260Arg	missense	Exon 7 of 7	ENSP00000439402.1
	ZNF667	ENST00000292069.10	TSL:1	c.779A>G	p.Lys260Arg	missense	Exon 5 of 5	ENSP00000292069.5
	ZNF667	ENST00000909113.1		c.779A>G	p.Lys260Arg	missense	Exon 5 of 5	ENSP00000579172.1

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

GnomAD2 exomes AF: 0.575 AC: 144269 AN: 250930 AF XY: 0.569

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 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

African (AFR) AF: 0.518 AC: 17341 AN: 33480

American (AMR) AF: 0.643 AC: 28759 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 11486 AN: 26132

East Asian (EAS) AF: 0.884 AC: 35091 AN: 39686

South Asian (SAS) AF: 0.597 AC: 51508 AN: 86242

European-Finnish (FIN) AF: 0.611 AC: 32611 AN: 53402

Middle Eastern (MID) AF: 0.416 AC: 2400 AN: 5768

European-Non Finnish (NFE) AF: 0.517 AC: 575234 AN: 1111958

Other (OTH) AF: 0.539 AC: 32544 AN: 60390

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

African (AFR) AF: 0.521 AC: 21604 AN: 41484

American (AMR) AF: 0.596 AC: 9113 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1501 AN: 3472

East Asian (EAS) AF: 0.881 AC: 4561 AN: 5176

South Asian (SAS) AF: 0.625 AC: 3008 AN: 4816

European-Finnish (FIN) AF: 0.607 AC: 6429 AN: 10588

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.519 AC: 35312 AN: 67974

Other (OTH) AF: 0.529 AC: 1116 AN: 2110

Alfa AF: 0.525 Hom.: 60447

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 v4.9

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
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	9.7e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.0
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.064
Sift	Benign	0.16	T
Sift4G	Uncertain	0.032	D
Polyphen		0.12	B
Vest4		0.055
MPC		0.091
ClinPred		0.0084	T
GERP RS		2.9
Varity_R		0.13
gMVP		0.023
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3760849; hg19: chr19-56953585; COSMIC: COSV107343620; COSMIC: COSV107343620;