Variant 16-30397356-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_001214909.2(ZNF48):c.106C>G(p.Gln36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Consequence

ZNF48
NM_001214909.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0870

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=0.04861003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF48	NM_001214909.2 linkuse as main transcript	c.106C>G	p.Gln36Glu	missense_variant	3/3	ENST00000613509.2	NP_001201838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF48	ENST00000613509.2 linkuse as main transcript	c.106C>G	p.Gln36Glu	missense_variant	3/3	2	NM_001214909.2	ENSP00000480262	P1
ZNF48	ENST00000320159.2 linkuse as main transcript	c.106C>G	p.Gln36Glu	missense_variant	2/2	1		ENSP00000324056	P1
ZNF48	ENST00000528032.5 linkuse as main transcript	c.106C>G	p.Gln36Glu	missense_variant	3/3	4		ENSP00000435674
ZNF48	ENST00000622647.3 linkuse as main transcript	c.-264C>G		5_prime_UTR_variant	2/2	4		ENSP00000479658

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250760

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135526

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

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

Jul 27, 2021

The c.106C>G (p.Q36E) alteration is located in exon 3 (coding exon 2) of the ZNF48 gene. This alteration results from a C to G substitution at nucleotide position 106, causing the glutamine (Q) at amino acid position 36 to be replaced by a glutamic acid (E). 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

0.085

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.55

DANN

Benign

0.57

DEOGEN2

Benign

0.0024

T;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.51

T;T;T;.

M_CAP

Benign

0.0037

MetaRNN

Benign

0.049

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

.;.;N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.22

N;N;.;N

REVEL

Benign

0.066

Sift

Benign

0.72

T;T;.;D

Sift4G

Benign

0.74

T;T;T;T

Polyphen

0.0

.;.;B;B

Vest4

0.12, 0.12

MutPred

0.35

Gain of catalytic residue at Q36 (P = 0.0839);Gain of catalytic residue at Q36 (P = 0.0839);Gain of catalytic residue at Q36 (P = 0.0839);Gain of catalytic residue at Q36 (P = 0.0839);

MVP

0.055

MPC

0.43

ClinPred

0.033

GERP RS

1.4

Varity_R

0.075

gMVP

0.22

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