3-125232327-CTTTTTT-CTT

Variant names:

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

Variant summary

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

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. 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. 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
• 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.*10_*13delAAAA		3_prime_UTR	Exon 9 of 9	NP_068799.2	Q9UQR1-1
	ZNF148	NM_001348424.1		c.*10_*13delAAAA		3_prime_UTR	Exon 10 of 10	NP_001335353.1	Q9UQR1-1
	ZNF148	NM_001348425.2		c.*10_*13delAAAA		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.*10_*13delAAAA		splice_region	Exon 10 of 10	ENSP00000420448.1	Q9UQR1-1
	ZNF148	ENST00000360647.9	TSL:1 MANE Select	c.*10_*13delAAAA		3_prime_UTR	Exon 9 of 9	ENSP00000353863.4	Q9UQR1-1
	ZNF148	ENST00000484491.5	TSL:1	c.*10_*13delAAAA		3_prime_UTR	Exon 9 of 9	ENSP00000420335.1	Q9UQR1-1

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

GnomAD2 exomes AF: 0.00192 AC: 293 AN: 152218 AF XY: 0.00211

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 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

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

African (AFR) AF: 0.000240 AC: 7 AN: 29124

American (AMR) AF: 0.000706 AC: 25 AN: 35398

Ashkenazi Jewish (ASJ) AF: 0.000496 AC: 11 AN: 22194

East Asian (EAS) AF: 0.000237 AC: 9 AN: 37988

South Asian (SAS) AF: 0.000532 AC: 39 AN: 73374

European-Finnish (FIN) AF: 0.000723 AC: 29 AN: 40126

Middle Eastern (MID) AF: 0.000398 AC: 2 AN: 5020

European-Non Finnish (NFE) AF: 0.000160 AC: 164 AN: 1023672

Other (OTH) AF: 0.000219 AC: 12 AN: 54726

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

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

African (AFR) AF: 0.00 AC: 0 AN: 39776

American (AMR) AF: 0.00 AC: 0 AN: 14710

Ashkenazi Jewish (ASJ) AF: 0.000293 AC: 1 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: 9262

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66500

Other (OTH) AF: 0.000495 AC: 1 AN: 2020

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00226 Hom.: 1354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

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

Other links and lift over

dbSNP: rs35950048; hg19: chr3-124951171;