NM_144976.4:c.1622C>G

Variant names:

• chr19-12526486-G-C
• rs1392677470
• NM_144976.4:c.1622C>G

Variant summary

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

The NM_144976.4(ZNF564):​c.1622C>G​(p.Ser541*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF564 NM_144976.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747
• 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF564	NM_144976.4	c.1622C>G	p.Ser541*	stop_gained	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.1622C>G	p.Ser541*	stop_gained	Exon 4 of 4	1	NM_144976.4	ENSP00000340004.6
ENSG00000269693	ENST00000593682.1	n.*4600C>G		non_coding_transcript_exon_variant	Exon 4 of 4	1		ENSP00000473043.1
ENSG00000269693	ENST00000593682.1	n.*4600C>G		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000473043.1
ENSG00000196826	ENST00000428311.1	c.3+24844C>G		intron_variant	Intron 1 of 3	2		ENSP00000404127.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454342 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723260

African (AFR) AF: 0.00 AC: 0 AN: 32896

American (AMR) AF: 0.00 AC: 0 AN: 42862

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25810

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00 AC: 0 AN: 84948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109238

Other (OTH) AF: 0.0000167 AC: 1 AN: 60014

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	34
DANN	Benign	0.91
Eigen	Uncertain	0.24
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.0	N
PhyloP100		0.75
Vest4		0.025
GERP RS		-0.47
Mutation Taster		=174/26	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: rs1392677470; hg19: chr19-12637300;