rs17001730

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF700	NM_144566.3	c.961C>G	p.Leu321Val	missense_variant	Exon 4 of 4	ENST00000254321.10	NP_653167.1
ZNF700	NM_001271848.2	c.970C>G	p.Leu324Val	missense_variant	Exon 4 of 4		NP_001258777.1
ZNF69	XM_017027231.2	c.500-31056C>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.961C>G	p.Leu321Val	missense_variant	Exon 4 of 4	1	NM_144566.3	ENSP00000254321.4
ENSG00000267179	ENST00000590798.1	c.63+23712C>G		intron_variant	Intron 1 of 3	2		ENSP00000467286.1

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

GnomAD3 exomes AF: 0.000952 AC: 233 AN: 244820 Hom.: 2 AF XY: 0.000695 AC XY: 92 AN XY: 132450

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 SAS 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

Gnomad4 AFR exome AF: 0.0159

Gnomad4 AMR exome AF: 0.000305

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000354

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.000814

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

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00237

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 v4.3

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;T;T
MetaRNN	Benign	0.0060	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.90	N;.;.
REVEL	Benign	0.074
Sift	Benign	0.18	T;.;.
Sift4G	Uncertain	0.045	D;D;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

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: rs17001730; hg19: chr19-12059800;