19-12132954-C-A

Variant names:

• chr19-12132954-C-A
• rs777721501
• NM_021143.4:c.1232G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021143.4(ZNF20):​c.1232G>T​(p.Arg411Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. R411H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF20 NM_021143.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.12
• Publications: 3 publications found

Genes affected

ZNF20 (HGNC:12992): (zinc finger protein 20) 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]

ZNF625-ZNF20 (HGNC:48368): (ZNF625-ZNF20 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring zinc finger protein 625 (ZNF625) and zinc finger protein 20 (ZNF20) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ENSG00000290812 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08479351).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021143.4. 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
	ZNF20	NM_021143.4	MANE Select	c.1232G>T	p.Arg411Leu	missense	Exon 4 of 4	NP_066966.2	P17024
	ZNF20	NM_001203250.2		c.1223G>T	p.Arg408Leu	missense	Exon 4 of 4	NP_001190179.1
	ZNF625-ZNF20	NR_037802.1		n.1814G>T		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF20	ENST00000334213.10	TSL:1 MANE Select	c.1232G>T	p.Arg411Leu	missense	Exon 4 of 4	ENSP00000335437.5	P17024
	ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.*1263G>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000457423.1	F8WDT6
	ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.*1263G>T		3_prime_UTR	Exon 8 of 8	ENSP00000457423.1	F8WDT6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.2
DANN	Benign	0.87
DEOGEN2	Benign	0.071	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00020	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.070	N
PhyloP100		-4.1
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.058
Sift	Benign	0.049	D
Sift4G	Benign	0.14	T
Polyphen		0.21	B
Vest4		0.13
MutPred		0.54		Loss of MoRF binding (P = 0.0106)
MVP		0.21
MPC		0.23
ClinPred		0.18	T
GERP RS		-1.9
Varity_R		0.14
gMVP		0.033
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs777721501; hg19: chr19-12243769;