Variant 7-64336929-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001170905.3(ZNF736):c.173A>G(p.Gln58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,452,362 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ZNF736
NM_001170905.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.401

Variant links:

Genes affected

ZNF736 (HGNC:32467): (zinc finger protein 736) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF736 links:

ZNF736 (HGNC:):

ZNF736 links:

Genome browser will be placed here

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=0.15497419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF736	NM_001170905.3 linkuse as main transcript	c.173A>G	p.Gln58Arg	missense_variant	3/4	ENST00000423484.3	NP_001164376.1	B4DX44
ZNF736	NM_001294255.2 linkuse as main transcript	c.173A>G	p.Gln58Arg	missense_variant	3/3		NP_001281184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF736	ENST00000423484.3 linkuse as main transcript	c.173A>G	p.Gln58Arg	missense_variant	3/4	2	NM_001170905.3	ENSP00000400852.1	B4DX44
ZNF736	ENST00000355095.8 linkuse as main transcript	c.173A>G	p.Gln58Arg	missense_variant	4/5	5		ENSP00000347210.4	B4DX44
ZNF736	ENST00000488621.1 linkuse as main transcript	n.310A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000428

AC:

AN:

233858

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126840

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000962

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000551

AC:

AN:

1452362

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

721716

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:

0.00000723

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2024

The c.173A>G (p.Q58R) alteration is located in exon 4 (coding exon 3) of the ZNF736 gene. This alteration results from a A to G substitution at nucleotide position 173, causing the glutamine (Q) at amino acid position 58 to be replaced by an arginine (R). 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

0.098

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.029

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.043

T;.

M_CAP

Benign

0.0013

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.037

Sift

Uncertain

0.0010

D;D

Sift4G

Benign

0.094

T;T

Polyphen

0.66

P;P

Vest4

0.19

MutPred

0.44

Loss of ubiquitination at K60 (P = 0.0245);Loss of ubiquitination at K60 (P = 0.0245);

MVP

0.17

MPC

0.044

ClinPred

0.66

GERP RS

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.34

gMVP

0.016

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over