dbSNP rs374430658: ZNF700:p.Thr149Asn (chr19-11948470-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144566.3(ZNF700):c.446C>A(p.Thr149Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. T149I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF700
NM_144566.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

Variant links:

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]

ZNF700 links:

ENSG00000267179 (HGNC:):

ENSG00000267179 links:

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]

ZNF69 links:

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ACMG classification

Classification made for transcript

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=0.106898636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF700	NM_144566.3 link	c.446C>A	p.Thr149Asn	missense_variant	Exon 4 of 4	ENST00000254321.10	NP_653167.1	Q9H0M5
ZNF700	NM_001271848.2 link	c.455C>A	p.Thr152Asn	missense_variant	Exon 4 of 4		NP_001258777.1	Q9H0M5A0A087WVH9
ZNF69	XM_017027231.2 link	c.500-31571C>A		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 link	c.446C>A	p.Thr149Asn	missense_variant	Exon 4 of 4	1	NM_144566.3	ENSP00000254321.4		Q9H0M5
ENSG00000267179	ENST00000590798.1 link	c.63+23197C>A		intron_variant	Intron 1 of 3	2		ENSP00000467286.1		F5H0A9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727214

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.17

DANN

Benign

0.46

DEOGEN2

Benign

0.013

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00013

LIST_S2

Benign

0.047

T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;.;.

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.8

D;.;.

REVEL

Benign

0.057

Sift

Uncertain

0.026

D;.;.

Sift4G

Benign

0.088

T;T;T

Polyphen

0.021

B;.;.

Vest4

0.085

MutPred

0.41

Loss of phosphorylation at T149 (P = 0.0182);.;.;

MVP

0.20

MPC

0.0083

ClinPred

0.10

GERP RS

-1.3

Varity_R

0.074

gMVP

0.019

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over