Genetic Variant ZNF148:p.Ser658Ser (chr3-125232752-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_021964.3(ZNF148):c.1974C>T(p.Ser658Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.000599 in 1,613,880 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00055 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 5 hom. )

Consequence

ZNF148
NM_021964.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.18

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 3-125232752-G-A is Benign according to our data. Variant chr3-125232752-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 713344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF148	NM_021964.3 link	c.1974C>T	p.Ser658Ser	synonymous_variant	Exon 9 of 9	ENST00000360647.9	NP_068799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF148	ENST00000360647.9 link	c.1974C>T	p.Ser658Ser	synonymous_variant	Exon 9 of 9	1	NM_021964.3	ENSP00000353863.4		Q9UQR1-1

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000924

AC:

232

AN:

251024

Hom.:

AF XY:

0.000995

AC XY:

135

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000753

Gnomad ASJ exome

AF:

0.00517

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000947

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000943

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.000603

AC:

882

AN:

1461590

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

488

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00467

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000417

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.000552

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000962

Hom.:

Bravo

AF:

0.000654

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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