3-125232327-CTTTTTT-CTTTTTTT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• 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: Likely_benign. The variant received -4 ACMG points.

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

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

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

GnomAD2 exomes AF: 0.00466 AC: 710 AN: 152218 AF XY: 0.00466

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 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

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

African (AFR) AF: 0.00186 AC: 54 AN: 29058

American (AMR) AF: 0.00763 AC: 269 AN: 35250

Ashkenazi Jewish (ASJ) AF: 0.00614 AC: 136 AN: 22164

East Asian (EAS) AF: 0.0110 AC: 414 AN: 37538

South Asian (SAS) AF: 0.00637 AC: 465 AN: 73024

European-Finnish (FIN) AF: 0.00265 AC: 106 AN: 40032

Middle Eastern (MID) AF: 0.00400 AC: 20 AN: 5004

European-Non Finnish (NFE) AF: 0.00396 AC: 4029 AN: 1017236

Other (OTH) AF: 0.00459 AC: 250 AN: 54440

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

African (AFR) AF: 0.000150 AC: 6 AN: 39874

American (AMR) AF: 0.000475 AC: 7 AN: 14732

Ashkenazi Jewish (ASJ) AF: 0.00469 AC: 16 AN: 3414

East Asian (EAS) AF: 0.00220 AC: 11 AN: 5010

South Asian (SAS) AF: 0.000861 AC: 4 AN: 4644

European-Finnish (FIN) AF: 0.000324 AC: 3 AN: 9262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.000241 AC: 16 AN: 66486

Other (OTH) AF: 0.000491 AC: 1 AN: 2038

Alfa AF: 0.00532 Hom.: 1354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism

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;