19-11948880-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144566.3(ZNF700):c.856G>A(p.Ala286Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF700 NM_144566.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0770

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17802054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF700	NM_144566.3	c.856G>A	p.Ala286Thr	missense_variant	4/4	ENST00000254321.10
ZNF700	NM_001271848.2	c.865G>A	p.Ala289Thr	missense_variant	4/4
ZNF69	XM_017027231.2	c.500-31161G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF700	ENST00000254321.10	c.856G>A	p.Ala286Thr	missense_variant	4/4	1	NM_144566.3	P2
	ENST00000586394.1	n.69-4102G>A		intron_variant, non_coding_transcript_variant		3
ZNF700	ENST00000622593.4	c.865G>A	p.Ala289Thr	missense_variant	4/4	4		A2
ZNF700	ENST00000482090.1	c.802G>A	p.Ala268Thr	missense_variant	3/3	2		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451300 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 721970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.856G>A (p.A286T) alteration is located in exon 4 (coding exon 4) of the ZNF700 gene. This alteration results from a G to A substitution at nucleotide position 856, causing the alanine (A) at amino acid position 286 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	13
Dann	Benign	0.97
DEOGEN2	Benign	0.019	T;.;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.44	N;.;.
MutationTaster	Benign	1.0	N;N;D
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.3	D;.;.
REVEL	Benign	0.056
Sift	Benign	0.17	T;.;.
Sift4G	Benign	0.63	T;T;T
Polyphen		0.99	D;.;.
Vest4		0.10
MutPred		0.38		Gain of phosphorylation at A286 (P = 0.1199);.;.;
MVP		0.23
MPC		0.040
ClinPred		0.42	T
GERP RS		0.67
Varity_R		0.083
gMVP		0.0046

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-12059695;