Variant 16-30397537-G-A 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_001214909.2(ZNF48):c.287G>A(p.Arg96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,826 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ZNF48
NM_001214909.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0380

Variant links:

Genes affected

ZNF48 (HGNC:13114): (zinc finger protein 48) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF48 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=0.05713585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF48	NM_001214909.2 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	3/3	ENST00000613509.2	NP_001201838.1	Q96MX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF48	ENST00000613509.2 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	3/3	2	NM_001214909.2	ENSP00000480262.1	Q96MX3
ZNF48	ENST00000320159.2 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	2/2	1		ENSP00000324056.2	Q96MX3
ZNF48	ENST00000528032.5 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	3/3	4		ENSP00000435674.1	E9PJ50
ZNF48	ENST00000622647 linkuse as main transcript	c.-83G>A		5_prime_UTR_variant	2/2	4		ENSP00000479658.1	A0A087WVT1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251258

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135836

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

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

Feb 06, 2023

The c.287G>A (p.R96Q) alteration is located in exon 3 (coding exon 2) of the ZNF48 gene. This alteration results from a G to A substitution at nucleotide position 287, causing the arginine (R) at amino acid position 96 to be replaced by a glutamine (Q). 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

0.092

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

T;T;T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.20

T;T;T;.

M_CAP

Benign

0.0076

MetaRNN

Benign

0.057

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

.;.;N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.3

N;N;.;N

REVEL

Benign

0.034

Sift

Benign

0.23

T;T;.;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.0020

.;.;B;B

Vest4

0.091

MutPred

0.31

Loss of MoRF binding (P = 0.0491);Loss of MoRF binding (P = 0.0491);Loss of MoRF binding (P = 0.0491);Loss of MoRF binding (P = 0.0491);

MVP

0.13

MPC

0.45

ClinPred

0.038

GERP RS

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.038

gMVP

0.27

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