rs778511183

Variant names:

• chr19-21034179-C-T
• rs778511183
• NM_025189.4:c.317C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-21034179-C-T
• chr19-21034179-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_025189.4(ZNF430):​c.317C>T​(p.Pro106Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,593,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: ZNF430 NM_025189.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.950
• Publications: 0 publications found

Genes affected

ZNF430 (HGNC:20808): (zinc finger protein 430) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in substantia nigra development. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17065537).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025189.4. 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
	ZNF430	NM_025189.4	MANE Select	c.317C>T	p.Pro106Leu	missense	Exon 4 of 5	NP_079465.3
	ZNF430	NM_001172671.2		c.314C>T	p.Pro105Leu	missense	Exon 4 of 5	NP_001166142.1	Q2NKJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF430	ENST00000261560.10	TSL:1 MANE Select	c.317C>T	p.Pro106Leu	missense	Exon 4 of 5	ENSP00000261560.4	Q9H8G1
	ZNF430	ENST00000935026.1		c.224C>T	p.Pro75Leu	missense	Exon 3 of 4	ENSP00000605085.1
	ZNF430	ENST00000594110.5	TSL:4	c.317C>T	p.Pro106Leu	missense	Exon 4 of 5	ENSP00000473069.1	M0R392

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000205 AC: 5 AN: 244476 AF XY: 0.0000226

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000451

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000119 AC: 171 AN: 1441664 Hom.: 0 Cov.: 29 AF XY: 0.000116 AC XY: 83 AN XY: 717244

African (AFR) AF: 0.0000304 AC: 1 AN: 32846

American (AMR) AF: 0.00 AC: 0 AN: 43782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25464

East Asian (EAS) AF: 0.00 AC: 0 AN: 39222

South Asian (SAS) AF: 0.00 AC: 0 AN: 82874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.000153 AC: 168 AN: 1100242

Other (OTH) AF: 0.0000337 AC: 2 AN: 59364

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74288

African (AFR) AF: 0.0000241 AC: 1 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.3
DANN	Benign	0.97
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.35	N
PhyloP100		-0.95
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-7.4	D
REVEL	Benign	0.045
Sift	Uncertain	0.026	D
Sift4G	Benign	0.17	T
Polyphen		0.054	B
Vest4		0.40
MutPred		0.53		Loss of disorder (P = 0.0267)
MVP		0.10
MPC		0.39
ClinPred		0.28	T
GERP RS		0.20
Varity_R		0.11
gMVP		0.034
Mutation Taster		=99/1	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: rs778511183; hg19: chr19-21216985;