chr3-125232327-CTT-C

Variant names:

• chr3-125232327-CTT-C
• rs35950048
• ENST00000485866.5:c.*12_*13delAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000485866.5(ZNF148):​c.*12_*13delAA variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,255,042 control chromosomes in the GnomAD database, including 3 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0036 (0 hom., cov: 0)
  • Exomes 𝑓: 0.14 (3 hom.)
• Consequence: ZNF148 ENST00000485866.5 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF148	NM_021964.3	c.*12_*13delAA		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	c.*12_*13delAA		3_prime_UTR_variant	Exon 9 of 9	1	NM_021964.3	ENSP00000353863.4

Frequencies

GnomAD3 genomes AF: 0.00356 AC: 521 AN: 146306 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00368

Gnomad ASJ AF: 0.00499

Gnomad EAS AF: 0.000398

Gnomad SAS AF: 0.000430

Gnomad FIN AF: 0.0125

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.00401

Gnomad OTH AF: 0.00298

GnomAD3 exomes AF: 0.248 AC: 37680 AN: 152218 Hom.: 2 AF XY: 0.254 AC XY: 21215 AN XY: 83400

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.142 AC: 157503 AN: 1108662 Hom.: 3 AF XY: 0.147 AC XY: 80506 AN XY: 549358

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.0829

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.00358 AC: 524 AN: 146380 Hom.: 0 Cov.: 0 AF XY: 0.00381 AC XY: 271 AN XY: 71066

Gnomad4 AFR AF: 0.00148

Gnomad4 AMR AF: 0.00367

Gnomad4 ASJ AF: 0.00499

Gnomad4 EAS AF: 0.000399

Gnomad4 SAS AF: 0.000431

Gnomad4 FIN AF: 0.0125

Gnomad4 NFE AF: 0.00401

Gnomad4 OTH AF: 0.00394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs35950048; hg19: chr3-124951171;