Variant 16-30534277-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001305018.2(ZNF747):c.263G>A(p.Trp88Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,441,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF747
NM_001305018.2 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.570

Variant links:

Genes affected

ZNF747 (HGNC:28350): (zinc finger protein 747) Predicted to enable metal ion binding activity. Predicted to be involved in regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

ZNF747 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF747	NM_001305018.2 linkuse as main transcript	c.263G>A	p.Trp88Ter	stop_gained	2/3	ENST00000693075.1	NP_001291947.1
ZNF747	NM_001305019.2 linkuse as main transcript	c.263G>A	p.Trp88Ter	stop_gained	2/3		NP_001291948.1
ZNF747	NM_023931.4 linkuse as main transcript	c.403G>A	p.Gly135Arg	missense_variant	1/2		NP_076420.1
ZNF747	NM_001305020.2 linkuse as main transcript	c.403G>A	p.Gly135Arg	missense_variant	1/2		NP_001291949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF747	ENST00000693075.1 linkuse as main transcript	c.263G>A	p.Trp88Ter	stop_gained	2/3		NM_001305018.2	ENSP00000509633	A2
ZNF747	ENST00000252799.3 linkuse as main transcript	c.403G>A	p.Gly135Arg	missense_variant	1/2	1		ENSP00000252799		Q9BV97-1
ZNF747	ENST00000395094.3 linkuse as main transcript	c.403G>A	p.Gly135Arg	missense_variant	1/2	1		ENSP00000378528		Q9BV97-2
ZNF747	ENST00000568028.1 linkuse as main transcript	c.263G>A	p.Trp88Ter	stop_gained	2/3	2		ENSP00000457274	P4	Q9BV97-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1441144

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715134

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:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 23, 2024

The c.403G>A (p.G135R) alteration is located in exon 1 (coding exon 1) of the ZNF747 gene. This alteration results from a G to A substitution at nucleotide position 403, causing the glycine (G) at amino acid position 135 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

0.30

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

A;A;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.54

N;N

REVEL

Benign

0.090

Sift

Benign

0.062

T;D

Sift4G

Uncertain

0.016

D;T

Polyphen

1.0

D;D

Vest4

0.35

MutPred

0.30

Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);

MVP

0.28

MPC

0.52

ClinPred

0.92

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.099

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.47

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.47

Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over