19-43607864-C-T

Variant names:

• chr19-43607864-C-T
• rs947950020
• NM_182498.4:c.320G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182498.4(ZNF428):​c.320G>A​(p.Gly107Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,403,158 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G107A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF428 NM_182498.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41
• Publications: 0 publications found

Genes affected

ZNF428 (HGNC:20804): (zinc finger protein 428) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SRRM5 (HGNC:37248): (serine/arginine repetitive matrix 5)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182498.4. 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
	ZNF428	NM_182498.4	MANE Select	c.320G>A	p.Gly107Glu	missense	Exon 3 of 3	NP_872304.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF428	ENST00000300811.8	TSL:1 MANE Select	c.320G>A	p.Gly107Glu	missense	Exon 3 of 3	ENSP00000300811.2	Q96B54
	ZNF428	ENST00000855579.1		c.419G>A	p.Gly140Glu	missense	Exon 4 of 4	ENSP00000525638.1
	ZNF428	ENST00000855581.1		c.419G>A	p.Gly140Glu	missense	Exon 5 of 5	ENSP00000525640.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 155102 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1403158 Hom.: 0 Cov.: 36 AF XY: 0.00000289 AC XY: 2 AN XY: 692710

African (AFR) AF: 0.00 AC: 0 AN: 31988

American (AMR) AF: 0.00 AC: 0 AN: 35734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24828

East Asian (EAS) AF: 0.00 AC: 0 AN: 36408

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48910

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5610

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081308

Other (OTH) AF: 0.0000172 AC: 1 AN: 58150

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.57	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.30	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.36		Loss of catalytic residue at G107 (P = 0.0064)
MVP		0.54
MPC		0.90
ClinPred		1.0	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.77
gMVP		0.66
Mutation Taster		=85/15	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: rs947950020; hg19: chr19-44112016;