NM_144976.4:c.1142G>T

Variant names:

• chr19-12526966-C-A
• rs370610215
• NM_144976.4:c.1142G>T

Variant summary

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

The NM_144976.4(ZNF564):​c.1142G>T​(p.Arg381Leu) 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. 13/21 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. R381Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF564 NM_144976.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 0 publications found

Genes affected

ZNF564 (HGNC:31106): (zinc finger protein 564) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269693 (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=0.17935053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF564	NM_144976.4	c.1142G>T	p.Arg381Leu	missense_variant	Exon 4 of 4	ENST00000339282.12	NP_659413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF564	ENST00000339282.12	c.1142G>T	p.Arg381Leu	missense_variant	Exon 4 of 4	1	NM_144976.4	ENSP00000340004.6
ENSG00000269693	ENST00000593682.1	n.*4120G>T		non_coding_transcript_exon_variant	Exon 4 of 4	1		ENSP00000473043.1
ENSG00000269693	ENST00000593682.1	n.*4120G>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000473043.1
ENSG00000196826	ENST00000428311.1	c.3+24364G>T		intron_variant	Intron 1 of 3	2		ENSP00000404127.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.68	N
PhyloP100		-2.8
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.091
Sift	Benign	0.074	T
Sift4G	Benign	0.19	T
Polyphen		0.58	P
Vest4		0.13
MutPred		0.63		Loss of disorder (P = 0.0452);
MVP		0.14
MPC		0.67
ClinPred		0.56	D
GERP RS		-2.4
Varity_R		0.15
gMVP		0.063
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs370610215; hg19: chr19-12637780;