NM_003442.6:c.1687-3668T>G

Variant names:

• chr11-9521572-T-G
• rs4910472
• NM_003442.6:c.1687-3668T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003442.6(ZNF143):​c.1687-3668T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 148,018 control chromosomes in the GnomAD database, including 11,689 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (11689 hom., cov: 30)
• Consequence: ZNF143 NM_003442.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 1 publications found

Genes affected

ZNF143 (HGNC:12928): (zinc finger protein 143) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of snRNA transcription by RNA polymerase II. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF143 Gene-Disease associations (from GenCC):

• methylmalonic aciduria and homocystinuria

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003442.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF143	NM_003442.6	MANE Select	c.1687-3668T>G		intron	N/A	NP_003433.3
	ZNF143	NM_001282656.2		c.1684-3668T>G		intron	N/A	NP_001269585.1
	ZNF143	NM_001282657.2		c.1594-3668T>G		intron	N/A	NP_001269586.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF143	ENST00000396602.7	TSL:1 MANE Select	c.1687-3668T>G		intron	N/A	ENSP00000379847.2
	ZNF143	ENST00000530463.5	TSL:1	c.1684-3668T>G		intron	N/A	ENSP00000432154.1
	ZNF143	ENST00000396604.5	TSL:5	c.1684-3668T>G		intron	N/A	ENSP00000379849.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 58610 AN: 147916 Hom.: 11679 Cov.: 30

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.477

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.424

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.396 AC: 58646 AN: 148018 Hom.: 11689 Cov.: 30 AF XY: 0.388 AC XY: 28033 AN XY: 72296

African (AFR) AF: 0.320 AC: 12651 AN: 39494

American (AMR) AF: 0.412 AC: 6163 AN: 14974

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1894 AN: 3426

East Asian (EAS) AF: 0.332 AC: 1688 AN: 5080

South Asian (SAS) AF: 0.361 AC: 1698 AN: 4702

European-Finnish (FIN) AF: 0.338 AC: 3369 AN: 9970

Middle Eastern (MID) AF: 0.469 AC: 135 AN: 288

European-Non Finnish (NFE) AF: 0.444 AC: 29799 AN: 67148

Other (OTH) AF: 0.426 AC: 866 AN: 2034

Alfa AF: 0.398 Hom.: 1533

Bravo AF: 0.395

Asia WGS AF: 0.347 AC: 1204 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.38
PhyloP100		0.19
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: rs4910472; hg19: chr11-9543119;