Variant 3-125232977-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021964.3(ZNF148):c.1749G>A(p.Pro583=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,613,580 control chromosomes in the GnomAD database, including 451,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45736 hom., cov: 31)

Exomes 𝑓: 0.74 ( 406103 hom. )

Consequence

ZNF148
NM_021964.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0800

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 3-125232977-C-T is Benign according to our data. Variant chr3-125232977-C-T is described in ClinVar as [Benign]. Clinvar id is 1274027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF148	NM_021964.3 linkuse as main transcript	c.1749G>A	p.Pro583=	synonymous_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.1749G>A	p.Pro583=	synonymous_variant	9/9	1	NM_021964.3	ENSP00000353863	P1	Q9UQR1-1

Frequencies

GnomAD3 genomes

AF:

0.771

AC:

117142

AN:

151946

Hom.:

45710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.853

Gnomad AMI

AF:

0.815

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.826

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.665

Gnomad FIN

AF:

0.771

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.783

GnomAD3 exomes

AF:

0.712

AC:

178538

AN:

250768

Hom.:

65079

AF XY:

0.718

AC XY:

97286

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.852

Gnomad AMR exome

AF:

0.543

Gnomad ASJ exome

AF:

0.825

Gnomad EAS exome

AF:

0.509

Gnomad SAS exome

AF:

0.678

Gnomad FIN exome

AF:

0.763

Gnomad NFE exome

AF:

0.764

Gnomad OTH exome

AF:

0.750

GnomAD4 exome

AF:

0.742

AC:

1084967

AN:

1461516

Hom.:

406103

Cov.:

AF XY:

0.743

AC XY:

539877

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.864

Gnomad4 AMR exome

AF:

0.562

Gnomad4 ASJ exome

AF:

0.827

Gnomad4 EAS exome

AF:

0.493

Gnomad4 SAS exome

AF:

0.680

Gnomad4 FIN exome

AF:

0.761

Gnomad4 NFE exome

AF:

0.756

Gnomad4 OTH exome

AF:

0.751

GnomAD4 genome

AF:

0.771

AC:

117222

AN:

152064

Hom.:

45736

Cov.:

AF XY:

0.767

AC XY:

57004

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.852

Gnomad4 AMR

AF:

0.689

Gnomad4 ASJ

AF:

0.826

Gnomad4 EAS

AF:

0.503

Gnomad4 SAS

AF:

0.664

Gnomad4 FIN

AF:

0.771

Gnomad4 NFE

AF:

0.763

Gnomad4 OTH

AF:

0.782

Alfa

AF:

0.764

Hom.:

71425

Bravo

AF:

0.765

Asia WGS

AF:

0.628

AC:

2182

AN:

3476

EpiCase

AF:

0.764

EpiControl

AF:

0.769

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 18, 2019	- -

Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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