3-125232327-CTTTTTT-CTTTTTTT

Variant names:

• chr3-125232327-C-CT
• rs35950048
• ENST00000485866.5:c.*13dupA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000485866.5(ZNF148):​c.*13dupA variant causes a splice region change involving the alteration of a non-conserved nucleotide. 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 0.00053 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0044 (0 hom.)
• Consequence: ZNF148 ENST00000485866.5 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 78 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000525 AC: 77 AN: 146558 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000126

Gnomad AMI AF: 0.0157

Gnomad AMR AF: 0.000476

Gnomad ASJ AF: 0.00469

Gnomad EAS AF: 0.00219

Gnomad SAS AF: 0.000860

Gnomad FIN AF: 0.000324

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000241

Gnomad OTH AF: 0.000495

GnomAD3 exomes AF: 0.00466 AC: 710 AN: 152218 Hom.: 0 AF XY: 0.00466 AC XY: 389 AN XY: 83400

Gnomad AFR exome AF: 0.00152

Gnomad AMR exome AF: 0.00908

Gnomad ASJ exome AF: 0.00537

Gnomad EAS exome AF: 0.0106

Gnomad SAS exome AF: 0.00601

Gnomad FIN exome AF: 0.00309

Gnomad NFE exome AF: 0.00276

Gnomad OTH exome AF: 0.00218

GnomAD4 exome AF: 0.00437 AC: 5743 AN: 1313746 Hom.: 0 Cov.: 0 AF XY: 0.00441 AC XY: 2865 AN XY: 649384

Gnomad4 AFR exome AF: 0.00186

Gnomad4 AMR exome AF: 0.00763

Gnomad4 ASJ exome AF: 0.00614

Gnomad4 EAS exome AF: 0.0110

Gnomad4 SAS exome AF: 0.00637

Gnomad4 FIN exome AF: 0.00265

Gnomad4 NFE exome AF: 0.00396

Gnomad4 OTH exome AF: 0.00459

GnomAD4 genome AF: 0.000532 AC: 78 AN: 146632 Hom.: 0 Cov.: 0 AF XY: 0.000505 AC XY: 36 AN XY: 71222

Gnomad4 AFR AF: 0.000150

Gnomad4 AMR AF: 0.000475

Gnomad4 ASJ AF: 0.00469

Gnomad4 EAS AF: 0.00220

Gnomad4 SAS AF: 0.000861

Gnomad4 FIN AF: 0.000324

Gnomad4 NFE AF: 0.000241

Gnomad4 OTH AF: 0.000491

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;