Variant 16-30534270-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 ENST00000252799.3(ZNF747):c.410G>A(p.Arg137Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF747
ENST00000252799.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.242

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:

Genome browser will be placed here

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=0.034408808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF747	NM_001305018.2 linkuse as main transcript	c.270G>A	p.Glu90=	synonymous_variant	2/3	ENST00000693075.1	NP_001291947.1
ZNF747	NM_023931.4 linkuse as main transcript	c.410G>A	p.Arg137Lys	missense_variant	1/2		NP_076420.1
ZNF747	NM_001305020.2 linkuse as main transcript	c.410G>A	p.Arg137Lys	missense_variant	1/2		NP_001291949.1
ZNF747	NM_001305019.2 linkuse as main transcript	c.270G>A	p.Glu90=	synonymous_variant	2/3		NP_001291948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF747	ENST00000252799.3 linkuse as main transcript	c.410G>A	p.Arg137Lys	missense_variant	1/2	1		ENSP00000252799		Q9BV97-1
ZNF747	ENST00000395094.3 linkuse as main transcript	c.410G>A	p.Arg137Lys	missense_variant	1/2	1		ENSP00000378528		Q9BV97-2
ZNF747	ENST00000693075.1 linkuse as main transcript	c.270G>A	p.Glu90=	synonymous_variant	2/3		NM_001305018.2	ENSP00000509633	A2
ZNF747	ENST00000568028.1 linkuse as main transcript	c.270G>A	p.Glu90=	synonymous_variant	2/3	2		ENSP00000457274	P4	Q9BV97-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000918

AC:

AN:

217892

Hom.:

AF XY:

0.00

AC XY:

AN XY:

118082

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000126

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717338

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Apr 23, 2024

The c.410G>A (p.R137K) 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 410, causing the arginine (R) at amino acid position 137 to be replaced by a lysine (K). 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

0.21

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.5

DANN

Benign

0.97

DEOGEN2

Benign

0.0090

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.21

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.22

N;N

REVEL

Benign

0.0080

Sift

Benign

0.058

T;D

Sift4G

Benign

0.35

T;T

Polyphen

0.0050

B;B

Vest4

0.11

MutPred

0.34

Gain of methylation at R137 (P = 0.0116);Gain of methylation at R137 (P = 0.0116);

MVP

0.040

MPC

0.25

ClinPred

0.036

GERP RS

1.5

Varity_R

0.16

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