Variant 3-125232454-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_021964.3(ZNF148):c.2272C>T(p.Arg758Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF148
NM_021964.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.18

Variant links:

Genes affected

ZNF148 (HGNC:12933): (zinc finger protein 148) The protein encoded by this gene is a member of the Kruppel family of zinc finger DNA binding proteins. The encoded protein activates transcription of the T-cell receptor and intestinal alkaline phosphatase genes but represses transcription of the ornithine decarboxylase, vimentin, gastrin, stomelysin, and enolase genes. Increased expression of this gene results in decreased patient survival rates from colorectal cancer, while mutations in this gene have been associated with global developmental delay, hypoplastic corpus callosum, and dysmorphic facies. [provided by RefSeq, Feb 2017]

ZNF148 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZNF148. . Gene score misZ 3.5168 (greater than the threshold 3.09). Trascript score misZ 4.5786 (greater than threshold 3.09). GenCC has associacion of gene with global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF148	NM_021964.3 linkuse as main transcript	c.2272C>T	p.Arg758Trp	missense_variant	9/9	ENST00000360647.9	NP_068799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF148	ENST00000360647.9 linkuse as main transcript	c.2272C>T	p.Arg758Trp	missense_variant	9/9	1	NM_021964.3	ENSP00000353863	P1	Q9UQR1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461450

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727020

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:

8.99e-7

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 provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Apr 12, 2022

PM2, PP2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.88

D;T;D;D;D

Eigen

Benign

-0.091

Eigen_PC

Benign

0.082

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.96

.;D;.;.;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.52

D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;.;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.4

D;D;D;D;D

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D

Polyphen

0.0

B;B;B;B;B

Vest4

0.71

MutPred

0.59

Loss of disorder (P = 0.004);.;Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);Loss of disorder (P = 0.004);

MVP

0.42

MPC

1.9

ClinPred

0.97

GERP RS

3.5

Varity_R

0.55

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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