Variant 16-30534264-C-G 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_001305018.2(ZNF747):c.276G>C(p.Lys92Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,599,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

ZNF747
NM_001305018.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.291

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=0.018404305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF747	NM_001305018.2 linkuse as main transcript	c.276G>C	p.Lys92Asn	missense_variant	2/3	ENST00000693075.1	NP_001291947.1
ZNF747	NM_001305019.2 linkuse as main transcript	c.276G>C	p.Lys92Asn	missense_variant	2/3		NP_001291948.1
ZNF747	NM_023931.4 linkuse as main transcript	c.416G>C	p.Arg139Thr	missense_variant	1/2		NP_076420.1
ZNF747	NM_001305020.2 linkuse as main transcript	c.416G>C	p.Arg139Thr	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.276G>C	p.Lys92Asn	missense_variant	2/3		NM_001305018.2	ENSP00000509633	A2
ZNF747	ENST00000252799.3 linkuse as main transcript	c.416G>C	p.Arg139Thr	missense_variant	1/2	1		ENSP00000252799		Q9BV97-1
ZNF747	ENST00000395094.3 linkuse as main transcript	c.416G>C	p.Arg139Thr	missense_variant	1/2	1		ENSP00000378528		Q9BV97-2
ZNF747	ENST00000568028.1 linkuse as main transcript	c.276G>C	p.Lys92Asn	missense_variant	2/3	2		ENSP00000457274	P4	Q9BV97-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

221724

Hom.:

AF XY:

0.0000666

AC XY:

AN XY:

120098

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000743

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000187

AC:

AN:

1446924

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

718622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000602

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:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000743

AC:

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

Aug 17, 2022

The c.416G>C (p.R139T) alteration is located in exon 1 (coding exon 1) of the ZNF747 gene. This alteration results from a G to C substitution at nucleotide position 416, causing the arginine (R) at amino acid position 139 to be replaced by a threonine (T). 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

-0.61

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

M_CAP

Benign

0.0094

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-0.89

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-0.71

N;N

Sift

Benign

0.36

T;T

Sift4G

Benign

0.29

T;.

Vest4

0.27

MVP

0.072

ClinPred

0.11

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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