ENST00000485866.5:c.*10_*13delAAAA

Variant names:

• chr3-125232327-CTTTT-C
• rs35950048
• ENST00000485866.5:c.*10_*13delAAAA

Variant summary

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

The ENST00000485866.5(ZNF148):​c.*10_*13delAAAA variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,468,180 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 0.000014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: ZNF148 ENST00000485866.5 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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 GnomAdExome4 at 298 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF148	NM_021964.3	c.*10_*13delAAAA		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.*10_*13delAAAA		3_prime_UTR_variant	Exon 9 of 9	1	NM_021964.3	ENSP00000353863.4

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 146558 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000495

GnomAD3 exomes AF: 0.00192 AC: 293 AN: 152218 Hom.: 0 AF XY: 0.00211 AC XY: 176 AN XY: 83400

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00204

Gnomad EAS exome AF: 0.00109

Gnomad SAS exome AF: 0.00267

Gnomad FIN exome AF: 0.00203

Gnomad NFE exome AF: 0.00225

Gnomad OTH exome AF: 0.00191

GnomAD4 exome AF: 0.000225 AC: 298 AN: 1321622 Hom.: 0 AF XY: 0.000273 AC XY: 178 AN XY: 653146

Gnomad4 AFR exome AF: 0.000240

Gnomad4 AMR exome AF: 0.000706

Gnomad4 ASJ exome AF: 0.000496

Gnomad4 EAS exome AF: 0.000237

Gnomad4 SAS exome AF: 0.000532

Gnomad4 FIN exome AF: 0.000723

Gnomad4 NFE exome AF: 0.000160

Gnomad4 OTH exome AF: 0.000219

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 146558 Hom.: 0 Cov.: 0 AF XY: 0.0000141 AC XY: 1 AN XY: 71134

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000495

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;