NM_144566.3:c.628C>G

Variant names:

• chr19-11948652-C-G
• rs73509026
• NM_144566.3:c.628C>G

Variant summary

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

The NM_144566.3(ZNF700):​c.628C>G​(p.Arg210Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 1,611,612 control chromosomes in the GnomAD database, including 1,609 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R210Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.063 (471 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1138 hom.)
• Consequence: ZNF700 NM_144566.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 13 publications found

Genes affected

ZNF700 (HGNC:25292): (zinc finger protein 700) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ENSG00000267179 (HGNC:):

ZNF69 (HGNC:13138): (zinc finger protein 69) Enables identical protein binding activity. Predicted to be involved in negative 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=0.0018607676).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF700	NM_144566.3	c.628C>G	p.Arg210Gly	missense_variant	Exon 4 of 4	ENST00000254321.10	NP_653167.1
ZNF700	NM_001271848.2	c.637C>G	p.Arg213Gly	missense_variant	Exon 4 of 4		NP_001258777.1
ZNF69	XM_017027231.2	c.500-31389C>G		intron_variant	Intron 4 of 4		XP_016882720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF700	ENST00000254321.10	c.628C>G	p.Arg210Gly	missense_variant	Exon 4 of 4	1	NM_144566.3	ENSP00000254321.4
ENSG00000267179	ENST00000590798.1	c.63+23379C>G		intron_variant	Intron 1 of 3	2		ENSP00000467286.1

Frequencies

GnomAD3 genomes AF: 0.0632 AC: 9610 AN: 152046 Hom.: 469 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0417

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.0615

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0315

Gnomad OTH AF: 0.0593

GnomAD2 exomes AF: 0.0405 AC: 10077 AN: 248938 AF XY: 0.0394

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.0247

Gnomad ASJ exome AF: 0.0211

Gnomad EAS exome AF: 0.0259

Gnomad FIN exome AF: 0.0569

Gnomad NFE exome AF: 0.0326

Gnomad OTH exome AF: 0.0392

GnomAD4 exome AF: 0.0349 AC: 50948 AN: 1459448 Hom.: 1138 Cov.: 32 AF XY: 0.0350 AC XY: 25429 AN XY: 726058

African (AFR) AF: 0.134 AC: 4446 AN: 33180

American (AMR) AF: 0.0272 AC: 1193 AN: 43856

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 543 AN: 26074

East Asian (EAS) AF: 0.0257 AC: 1021 AN: 39682

South Asian (SAS) AF: 0.0397 AC: 3406 AN: 85716

European-Finnish (FIN) AF: 0.0547 AC: 2923 AN: 53404

Middle Eastern (MID) AF: 0.0565 AC: 325 AN: 5754

European-Non Finnish (NFE) AF: 0.0313 AC: 34826 AN: 1111498

Other (OTH) AF: 0.0376 AC: 2265 AN: 60284

GnomAD4 genome AF: 0.0632 AC: 9616 AN: 152164 Hom.: 471 Cov.: 33 AF XY: 0.0641 AC XY: 4771 AN XY: 74388

African (AFR) AF: 0.136 AC: 5632 AN: 41482

American (AMR) AF: 0.0417 AC: 637 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3470

East Asian (EAS) AF: 0.0220 AC: 114 AN: 5186

South Asian (SAS) AF: 0.0406 AC: 196 AN: 4824

European-Finnish (FIN) AF: 0.0615 AC: 651 AN: 10586

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0315 AC: 2142 AN: 68008

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0311 Hom.: 58

Bravo AF: 0.0638

TwinsUK AF: 0.0326 AC: 121

ALSPAC AF: 0.0358 AC: 138

ESP6500AA AF: 0.133 AC: 584

ESP6500EA AF: 0.0298 AC: 256

ExAC AF: 0.0434 AC: 5272

Asia WGS AF: 0.0290 AC: 103 AN: 3478

EpiCase AF: 0.0314

EpiControl AF: 0.0324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.062	T;.;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.000087	T;T;T
MetaRNN	Benign	0.0019	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.
PhyloP100		-1.2
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.9	D;.;.
REVEL	Benign	0.042
Sift	Uncertain	0.017	D;.;.
Sift4G	Benign	0.15	T;T;T
Polyphen		0.94	P;.;.
Vest4		0.11
MPC		0.024
ClinPred		0.038	T
GERP RS		0.55
Varity_R		0.24
gMVP		0.021
Mutation Taster		=99/1	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: rs73509026; hg19: chr19-12059467; COSMIC: COSV54315574; COSMIC: COSV54315574;