chr7-149474851-T-C

Position:

chr7-149474851-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001394198.1(ZNF746):c.1516A>G(p.Ser506Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,430,558 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ZNF746
NM_001394198.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.32

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04832357).

BP6

Variant 7-149474851-T-C is Benign according to our data. Variant chr7-149474851-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2362811.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF746	NM_001394198.1 linkuse as main transcript	c.1516A>G	p.Ser506Gly	missense_variant	7/7	ENST00000458143.7	NP_001381127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF746	ENST00000458143.7 linkuse as main transcript	c.1516A>G	p.Ser506Gly	missense_variant	7/7	2	NM_001394198.1	ENSP00000395007	A2
ZNF746	ENST00000340622.8 linkuse as main transcript	c.1468A>G	p.Ser490Gly	missense_variant	7/7	1		ENSP00000345140	P4	Q6NUN9-1
ZNF746	ENST00000644635.1 linkuse as main transcript	c.1513A>G	p.Ser505Gly	missense_variant	7/7			ENSP00000493970	A2
ZNF746	ENST00000685153.1 linkuse as main transcript	c.1471A>G	p.Ser491Gly	missense_variant	7/7			ENSP00000508891	A2	Q6NUN9-2

Frequencies

GnomAD3 genomes

AF:

0.0000465

AC:

AN:

150670

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000888

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000353

AC:

AN:

56648

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

33304

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:

0.0000839

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

177

AN:

1279888

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

628962

show subpopulations

Gnomad4 AFR exome

AF:

0.000122

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:

0.000169

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000465

AC:

AN:

150670

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

73578

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000888

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0010

DANN

Benign

0.32

DEOGEN2

Benign

0.012

.;T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.24

T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

.;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.030

.;N;N

REVEL

Benign

0.0020

Sift

Benign

0.54

.;T;T

Sift4G

Benign

0.73

.;T;T

Polyphen

0.0

.;B;B

Vest4

0.16, 0.15

MVP

0.15

MPC

0.54

ClinPred

0.013

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.026

gMVP

0.13

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