3-125289333-T-C

Position:

• chr3-125289333-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021964.3(ZNF148):​c.334-1105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,128 control chromosomes in the GnomAD database, including 45,741 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45741 hom., cov: 32)
• Consequence: ZNF148 NM_021964.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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	c.334-1105A>G		intron_variant		ENST00000360647.9	NP_068799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF148	ENST00000360647.9	c.334-1105A>G		intron_variant		1	NM_021964.3	ENSP00000353863.4

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117182 AN: 152010 Hom.: 45715 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.828

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.782

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.771 AC: 117262 AN: 152128 Hom.: 45741 Cov.: 32 AF XY: 0.767 AC XY: 57026 AN XY: 74360

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.782

Alfa AF: 0.751 Hom.: 6948

Bravo AF: 0.765

Asia WGS AF: 0.626 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9850300; hg19: chr3-125008177; COSMIC: COSV62303222;