rs4679372

Variant names:

• chr3-125229708-G-A
• rs4679372
• NM_021964.3:c.*2633C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021964.3(ZNF148):​c.*2633C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,028 control chromosomes in the GnomAD database, including 46,437 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 0.78 (46437 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ZNF148 NM_021964.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF148	NM_021964.3	c.*2633C>T		3_prime_UTR_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	c.*2633C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_021964.3	ENSP00000353863.4

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117951 AN: 151910 Hom.: 46408 Cov.: 31

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.784

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.776 AC: 118034 AN: 152028 Hom.: 46437 Cov.: 31 AF XY: 0.772 AC XY: 57362 AN XY: 74292

African (AFR) AF: 0.871 AC: 36166 AN: 41500

American (AMR) AF: 0.690 AC: 10537 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2867 AN: 3470

East Asian (EAS) AF: 0.502 AC: 2585 AN: 5150

South Asian (SAS) AF: 0.665 AC: 3203 AN: 4816

European-Finnish (FIN) AF: 0.770 AC: 8134 AN: 10566

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51905 AN: 67954

Other (OTH) AF: 0.784 AC: 1654 AN: 2110

Alfa AF: 0.765 Hom.: 55887

Bravo AF: 0.771

Asia WGS AF: 0.631 AC: 2195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.60
DANN	Benign	0.57
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4679372; hg19: chr3-124948552;