Genetic Variant ZNF701:p.Ser50Thr (chr19-52582207-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018260.3(ZNF701):c.148T>A(p.Ser50Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. S50A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ZNF701
NM_018260.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.224

Publications

0 publications found

Variant links:

Genes affected

ZNF701 (HGNC:25597): (zinc finger protein 701) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-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]

ZNF701 links:

ENSG00000268886 (HGNC:):

ENSG00000268886 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18618083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF701	NM_018260.3 link	c.148T>A	p.Ser50Thr	missense_variant	Exon 4 of 4	ENST00000391785.8	NP_060730.2	Q9NV72-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF701	ENST00000391785.8 link	c.148T>A	p.Ser50Thr	missense_variant	Exon 4 of 4	1	NM_018260.3	ENSP00000375662.2		Q9NV72-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1424962

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

705388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32214

American (AMR)

AF:

0.00

AC:

AN:

38148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24140

East Asian (EAS)

AF:

0.00

AC:

AN:

39286

South Asian (SAS)

AF:

0.00

AC:

AN:

80224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094324

Other (OTH)

AF:

0.0000170

AC:

AN:

58742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.011

.;.;T;.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.021

T;T;.;T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.19

T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.6

.;L;.;.;.

PhyloP100

0.22

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.5

.;N;N;.;N

REVEL

Benign

0.031

Sift

Uncertain

0.012

.;D;D;.;D

Sift4G

Benign

0.17

T;T;T;T;T

Vest4

0.14, 0.15, 0.13

MutPred

0.37

.;.;Loss of ubiquitination at K118 (P = 0.0618);Loss of ubiquitination at K118 (P = 0.0618);Loss of ubiquitination at K118 (P = 0.0618);

MVP

0.39

MPC

0.24

ClinPred

0.45

GERP RS

1.9

Varity_R

0.090

gMVP

0.027

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over