NM_021143.4:c.1232G>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF20	NM_021143.4	c.1232G>T	p.Arg411Leu	missense_variant	Exon 4 of 4	ENST00000334213.10	NP_066966.2
ZNF20	NM_001203250.2	c.1223G>T	p.Arg408Leu	missense_variant	Exon 4 of 4		NP_001190179.1
ZNF625-ZNF20	NR_037802.1	n.1814G>T		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF20	ENST00000334213.10	c.1232G>T	p.Arg411Leu	missense_variant	Exon 4 of 4	1	NM_021143.4	ENSP00000335437.5
ZNF625-ZNF20	ENST00000430024.5	n.*1263G>T		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000457423.1
ZNF625-ZNF20	ENST00000430024.5	n.*1263G>T		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000457423.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs777721501; hg19: chr19-12243769;