3-125232327-CTTTTTT-CT

Variant names:

• chr3-125232327-CTTTTT-C
• rs35950048
• ENST00000485866.5:c.*9_*13delAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000485866.5(ZNF148):​c.*9_*13delAAAAA variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,323,026 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF148 ENST00000485866.5 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000485866.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF148	NM_021964.3	MANE Select	c.*9_*13delAAAAA		3_prime_UTR	Exon 9 of 9	NP_068799.2	Q9UQR1-1
	ZNF148	NM_001348424.1		c.*9_*13delAAAAA		3_prime_UTR	Exon 10 of 10	NP_001335353.1	Q9UQR1-1
	ZNF148	NM_001348425.2		c.*9_*13delAAAAA		3_prime_UTR	Exon 10 of 10	NP_001335354.1	Q9UQR1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF148	ENST00000485866.5	TSL:1	c.*9_*13delAAAAA		splice_region	Exon 10 of 10	ENSP00000420448.1	Q9UQR1-1
	ZNF148	ENST00000360647.9	TSL:1 MANE Select	c.*9_*13delAAAAA		3_prime_UTR	Exon 9 of 9	ENSP00000353863.4	Q9UQR1-1
	ZNF148	ENST00000484491.5	TSL:1	c.*9_*13delAAAAA		3_prime_UTR	Exon 9 of 9	ENSP00000420335.1	Q9UQR1-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 146570 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000204 AC: 27 AN: 1323026 Hom.: 0 AF XY: 0.0000245 AC XY: 16 AN XY: 653846

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000343 AC: 1 AN: 29162

American (AMR) AF: 0.0000564 AC: 2 AN: 35458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22240

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 38010

South Asian (SAS) AF: 0.0000408 AC: 3 AN: 73472

European-Finnish (FIN) AF: 0.0000498 AC: 2 AN: 40176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5024

European-Non Finnish (NFE) AF: 0.0000156 AC: 16 AN: 1024704

Other (OTH) AF: 0.0000365 AC: 2 AN: 54780

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 146570 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 71138

African (AFR) AF: 0.00 AC: 0 AN: 39774

American (AMR) AF: 0.00 AC: 0 AN: 14714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 5028

South Asian (SAS) AF: 0.00 AC: 0 AN: 4652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66506

Other (OTH) AF: 0.00 AC: 0 AN: 2020

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35950048; hg19: chr3-124951171;