11-9471345-A-G

Position:

• chr11-9471345-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003442.6(ZNF143):​c.37A>G​(p.Met13Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,460,376 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: ZNF143 NM_003442.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF143	NM_003442.6	c.37A>G	p.Met13Val	missense_variant	2/16	ENST00000396602.7	NP_003433.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF143	ENST00000396602.7	c.37A>G	p.Met13Val	missense_variant	2/16	1	NM_003442.6	ENSP00000379847.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 249730 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135002

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1460376 Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17 AN XY: 726468

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000279

Gnomad4 OTH exome AF: 0.0000829

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;.;T;.;T;.;.;.;T;T;.;.;T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;.;D;D;D;D;T;D;D;D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.8	.;L;L;L;.;.;L;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N;N;N;N;N;N;N;D
REVEL	Benign	0.28
Sift	Benign	0.041	D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Benign	0.15	T;T;T;T;T;T;T;T;D;D;T;T;T;T
Polyphen		0.32, 0.45	.;.;B;.;.;.;B;.;.;.;.;.;.;.
Vest4		0.88, 0.85, 0.88, 0.79, 0.82
MVP		0.59
MPC		0.71
ClinPred		0.30	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs369233915; hg19: chr11-9492892;