NM_144566.3:c.961C>G

Variant names:

• chr19-11948985-C-G
• rs17001730
• NM_144566.3:c.961C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_144566.3(ZNF700):​c.961C>G​(p.Leu321Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000737 in 1,608,426 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.0039 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (11 hom.)
• Consequence: ZNF700 NM_144566.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0059915185).
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144566.3. 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
	ZNF700	NM_144566.3	MANE Select	c.961C>G	p.Leu321Val	missense	Exon 4 of 4	NP_653167.1
	ZNF700	NM_001271848.2		c.970C>G	p.Leu324Val	missense	Exon 4 of 4	NP_001258777.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF700	ENST00000254321.10	TSL:1 MANE Select	c.961C>G	p.Leu321Val	missense	Exon 4 of 4	ENSP00000254321.4
	ENSG00000267179	ENST00000590798.1	TSL:2	c.63+23712C>G		intron	N/A	ENSP00000467286.1
	ZNF700	ENST00000622593.4	TSL:4	c.970C>G	p.Leu324Val	missense	Exon 4 of 4	ENSP00000479449.1

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 595 AN: 152160 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000952 AC: 233 AN: 244820 AF XY: 0.000695

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.000217

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.000836

GnomAD4 exome AF: 0.000405 AC: 590 AN: 1456148 Hom.: 11 Cov.: 33 AF XY: 0.000341 AC XY: 247 AN XY: 724226

African (AFR) AF: 0.0159 AC: 523 AN: 32990

American (AMR) AF: 0.000305 AC: 13 AN: 42610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000354 AC: 3 AN: 84754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5750

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110854

Other (OTH) AF: 0.000814 AC: 49 AN: 60170

GnomAD4 genome AF: 0.00391 AC: 595 AN: 152278 Hom.: 4 Cov.: 33 AF XY: 0.00389 AC XY: 290 AN XY: 74464

African (AFR) AF: 0.0140 AC: 582 AN: 41554

American (AMR) AF: 0.000392 AC: 6 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000590 Hom.: 0

Bravo AF: 0.00429

ESP6500AA AF: 0.0129 AC: 57

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00114 AC: 139

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.071
DANN	Benign	0.79
DEOGEN2	Benign	0.062	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-2.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.074
Sift	Benign	0.18	T
Sift4G	Uncertain	0.045	D
Polyphen		0.0	B
Vest4		0.056
MVP		0.16
MPC		0.0083
ClinPred		0.011	T
GERP RS		-0.97
Varity_R		0.022
gMVP		0.013
Mutation Taster		=100/0	polymorphism

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: rs17001730; hg19: chr19-12059800;