Variant 7-149475132-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394198.1(ZNF746):c.1235G>A(p.Gly412Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000604 in 1,612,184 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

ZNF746
NM_001394198.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0360

Variant links:

Genes affected

ZNF746 (HGNC:21948): (zinc finger protein 746) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and ubiquitin protein ligase binding activity. Involved in negative regulation of transcription by RNA polymerase II; positive regulation of neuron death; and positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF746 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007679105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF746	NM_001394198.1 linkuse as main transcript	c.1235G>A	p.Gly412Glu	missense_variant	7/7	ENST00000458143.7	NP_001381127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF746	ENST00000458143.7 linkuse as main transcript	c.1235G>A	p.Gly412Glu	missense_variant	7/7	2	NM_001394198.1	ENSP00000395007.3	A0A8J9FQ52
ZNF746	ENST00000340622.8 linkuse as main transcript	c.1187G>A	p.Gly396Glu	missense_variant	7/7	1		ENSP00000345140.3	Q6NUN9-1
ZNF746	ENST00000644635.1 linkuse as main transcript	c.1232G>A	p.Gly411Glu	missense_variant	7/7			ENSP00000493970.1	A0A2R8YDQ5
ZNF746	ENST00000685153.1 linkuse as main transcript	c.1190G>A	p.Gly397Glu	missense_variant	7/7			ENSP00000508891.1	Q6NUN9-2

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000549

AC:

134

AN:

243878

Hom.:

AF XY:

0.000533

AC XY:

AN XY:

133188

show subpopulations

Gnomad AFR exome

AF:

0.000202

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000142

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.000507

GnomAD4 exome

AF:

0.000605

AC:

884

AN:

1460036

Hom.:

Cov.:

AF XY:

0.000566

AC XY:

411

AN XY:

726256

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000229

Gnomad4 NFE exome

AF:

0.000758

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000585

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000912

Hom.:

Bravo

AF:

0.000612

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000577

AC:

EpiCase

AF:

0.000981

EpiControl

AF:

0.00113

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

Jul 05, 2023

The c.1190G>A (p.G397E) alteration is located in exon 7 (coding exon 7) of the ZNF746 gene. This alteration results from a G to A substitution at nucleotide position 1190, causing the glycine (G) at amino acid position 397 to be replaced by a glutamic acid (E). 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

Pathogenic

0.60

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.0077

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

.;N;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.2

.;N;N

REVEL

Benign

0.088

Sift

Benign

0.25

.;T;T

Sift4G

Benign

0.33

.;T;T

Polyphen

0.31, 0.036

.;B;B

Vest4

0.13

MVP

0.33

MPC

1.4

ClinPred

0.014

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.46

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

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