3-125232327-CTTTTTT-CTTTTT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000485866.5(ZNF148):​c.*13delA 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. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (42657 hom., cov: 0)
  • Exomes 𝑓: 0.49 (5175 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF148 ENST00000485866.5 splice_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 3-125232327-CT-C is Benign according to our data. Variant chr3-125232327-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1179358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.762 AC: 111650 AN: 146492 Hom.: 42656 Cov.: 0

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.771

GnomAD2 exomes AF: 0.478 AC: 72728 AN: 152218 AF XY: 0.477

Gnomad AFR exome AF: 0.494

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.468

Gnomad FIN exome AF: 0.484

Gnomad NFE exome AF: 0.481

Gnomad OTH exome AF: 0.481

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.486 AC: 630036 AN: 1295878 Hom.: 5175 Cov.: 0 AF XY: 0.485 AC XY: 310898 AN XY: 640700

African (AFR) AF: 0.495 AC: 14358 AN: 28978

American (AMR) AF: 0.443 AC: 15258 AN: 34472

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 10721 AN: 22062

East Asian (EAS) AF: 0.463 AC: 16437 AN: 35524

South Asian (SAS) AF: 0.466 AC: 33466 AN: 71752

European-Finnish (FIN) AF: 0.477 AC: 18903 AN: 39650

Middle Eastern (MID) AF: 0.499 AC: 2489 AN: 4984

European-Non Finnish (NFE) AF: 0.490 AC: 492291 AN: 1004750

Other (OTH) AF: 0.486 AC: 26113 AN: 53706

GnomAD4 genome AF: 0.762 AC: 111684 AN: 146568 Hom.: 42657 Cov.: 0 AF XY: 0.758 AC XY: 53938 AN XY: 71188

African (AFR) AF: 0.845 AC: 33691 AN: 39858

American (AMR) AF: 0.686 AC: 10094 AN: 14708

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2768 AN: 3410

East Asian (EAS) AF: 0.511 AC: 2553 AN: 4994

South Asian (SAS) AF: 0.659 AC: 3058 AN: 4638

European-Finnish (FIN) AF: 0.734 AC: 6805 AN: 9274

Middle Eastern (MID) AF: 0.791 AC: 220 AN: 278

European-Non Finnish (NFE) AF: 0.755 AC: 50199 AN: 66474

Other (OTH) AF: 0.770 AC: 1570 AN: 2040

Alfa AF: 0.497 Hom.: 1354

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

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; COSMIC: COSV62301922; COSMIC: COSV62301922;