3-125232752-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_021964.3(ZNF148):c.1974C>T(p.Ser658=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.18

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF148	NM_021964.3	c.1974C>T	p.Ser658=	synonymous_variant	9/9	ENST00000360647.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF148	ENST00000360647.9	c.1974C>T	p.Ser658=	synonymous_variant	9/9	1	NM_021964.3	P1

Frequencies

GnomAD3 genomes AF: 0.000552 AC: 84 AN: 152172 Hom.: 2 Cov.: 32

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.: 1 AF XY: 0.000995 AC XY: 135 AN XY: 135658

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.: 5 Cov.: 74 AF XY: 0.000671 AC XY: 488 AN XY: 727108

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: 84 AN: 152290 Hom.: 2 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74464

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.: 0

Bravo AF: 0.000654

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs145231474; hg19: chr3-124951596; COSMIC: COSV62306556;