rs183038552

Variant names:

• chr19-43872784-C-A
• rs183038552
• NM_001033719.3:c.1430G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-43872784-C-A
• chr19-43872784-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001033719.3(ZNF404):​c.1430G>T​(p.Arg477Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R477H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ZNF404 NM_001033719.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

Genes affected

ZNF404 (HGNC:19417): (zinc finger protein 404) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037007928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF404	NM_001033719.3	c.1430G>T	p.Arg477Leu	missense_variant	Exon 3 of 3	ENST00000587539.2	NP_001028891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF404	ENST00000587539.2	c.1430G>T	p.Arg477Leu	missense_variant	Exon 3 of 3	5	NM_001033719.3	ENSP00000466051.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459102 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 725644

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000720

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.6
DANN	Benign	0.73
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00049	N
LIST_S2	Benign	0.14	T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.23	N;.
PrimateAI	Benign	0.31	T
REVEL	Benign	0.037
Sift4G	Benign	0.27	T;T
Polyphen		0.074	B;.
Vest4		0.25
MutPred		0.46		Loss of MoRF binding (P = 0.0024);.;
MVP		0.12
MPC		0.37
ClinPred		0.038	T
GERP RS		-2.5
Varity_R		0.083
gMVP		0.041

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs183038552; hg19: chr19-44376936;