chr3-125232327-CTTT-C

Variant names:

• chr3-125232327-CTTT-C
• rs35950048
• ENST00000485866.5:c.*11_*13delAAA

Variant summary

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

The ENST00000485866.5(ZNF148):​c.*11_*13delAAA variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,444,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0034 (0 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF148	NM_021964.3	c.*11_*13delAAA		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.*11_*13delAAA		3_prime_UTR_variant	Exon 9 of 9	1	NM_021964.3	ENSP00000353863.4

Frequencies

GnomAD3 genomes AF: 0.000109 AC: 16 AN: 146482 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000434

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000135

Gnomad OTH AF: 0.000496

GnomAD3 exomes AF: 0.0190 AC: 2890 AN: 152218 Hom.: 0 AF XY: 0.0201 AC XY: 1673 AN XY: 83400

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.0241

Gnomad EAS exome AF: 0.00937

Gnomad SAS exome AF: 0.0226

Gnomad FIN exome AF: 0.0223

Gnomad NFE exome AF: 0.0217

Gnomad OTH exome AF: 0.0182

GnomAD4 exome AF: 0.00335 AC: 4351 AN: 1298204 Hom.: 0 AF XY: 0.00403 AC XY: 2584 AN XY: 641316

Gnomad4 AFR exome AF: 0.00439

Gnomad4 AMR exome AF: 0.00910

Gnomad4 ASJ exome AF: 0.00784

Gnomad4 EAS exome AF: 0.00215

Gnomad4 SAS exome AF: 0.00802

Gnomad4 FIN exome AF: 0.00770

Gnomad4 NFE exome AF: 0.00256

Gnomad4 OTH exome AF: 0.00334

GnomAD4 genome AF: 0.000109 AC: 16 AN: 146558 Hom.: 0 Cov.: 0 AF XY: 0.000211 AC XY: 15 AN XY: 71182

Gnomad4 AFR AF: 0.0000502

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000434

Gnomad4 NFE AF: 0.000135

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;