3-125289333-T-C

Variant names:

• chr3-125289333-T-C
• rs9850300
• NM_021964.3:c.334-1105A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF148	NM_021964.3	c.334-1105A>G		intron_variant	Intron 4 of 8	ENST00000360647.9	NP_068799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF148	ENST00000360647.9	c.334-1105A>G		intron_variant	Intron 4 of 8	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

African (AFR) AF: 0.852 AC: 35393 AN: 41522

American (AMR) AF: 0.688 AC: 10507 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2868 AN: 3472

East Asian (EAS) AF: 0.502 AC: 2599 AN: 5176

South Asian (SAS) AF: 0.665 AC: 3208 AN: 4826

European-Finnish (FIN) AF: 0.770 AC: 8150 AN: 10580

Middle Eastern (MID) AF: 0.822 AC: 240 AN: 292

European-Non Finnish (NFE) AF: 0.764 AC: 51906 AN: 67970

Other (OTH) AF: 0.782 AC: 1648 AN: 2108

Alfa AF: 0.754 Hom.: 7240

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
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9850300; hg19: chr3-125008177; COSMIC: COSV62303222;