Genetic Variant ENST00000301093.6:c.103C>A (chr19-52572344-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000301093.6(ZNF701):c.103C>A(p.Arg35Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R35C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000088 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF701
ENST00000301093.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04344386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF701	NM_018260.3 link	c.-71-1733C>A		intron_variant	Intron 1 of 3	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.-71-1733C>A		intron_variant	Intron 1 of 3	1	NM_018260.3	ENSP00000375662.2		Q9NV72-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000782

AC:

AN:

127876

AF XY:

0.0000143

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000211

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000881

AC:

AN:

1135022

Hom.:

Cov.:

AF XY:

0.00000718

AC XY:

AN XY:

556900

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24362

American (AMR)

AF:

0.00

AC:

AN:

28164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15902

East Asian (EAS)

AF:

0.00

AC:

AN:

12808

South Asian (SAS)

AF:

0.00

AC:

AN:

76116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4388

European-Non Finnish (NFE)

AF:

0.00000870

AC:

AN:

919200

Other (OTH)

AF:

0.0000483

AC:

AN:

41442

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

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

0.21

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.63

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0020

T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.040

.;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-0.88

PhyloP100

-1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.34

N;.;N

REVEL

Benign

0.028

Sift

Pathogenic

0.0

D;.;D

Sift4G

Benign

0.26

T;T;T

Vest4

0.11

MutPred

0.23

Gain of glycosylation at R35 (P = 0.0306);Gain of glycosylation at R35 (P = 0.0306);Gain of glycosylation at R35 (P = 0.0306);

MVP

0.10

MPC

0.12

ClinPred

0.070

GERP RS

-0.28

Varity_R

0.18

gMVP

0.039

Mutation Taster

=100/0

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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ENST00000301093.6:c.103C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over