8-124977062-C-G

Variant names:

• chr8-124977062-C-G
• rs146940643
• NM_152412.3:c.794C>G

Variant summary

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

The NM_152412.3(ZNF572):​c.794C>G​(p.Thr265Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. T265I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF572 NM_152412.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 0 publications found

Genes affected

ZNF572 (HGNC:26758): (zinc finger protein 572) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.14589274).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152412.3. 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
	ZNF572	NM_152412.3	MANE Select	c.794C>G	p.Thr265Ser	missense	Exon 3 of 3	NP_689625.2	Q7Z3I7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF572	ENST00000319286.6	TSL:1 MANE Select	c.794C>G	p.Thr265Ser	missense	Exon 3 of 3	ENSP00000319305.5	Q7Z3I7
	ZNF572	ENST00000902451.1		c.794C>G	p.Thr265Ser	missense	Exon 3 of 3	ENSP00000572510.1
	ZNF572	ENST00000942607.1		c.794C>G	p.Thr265Ser	missense	Exon 3 of 3	ENSP00000612666.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459748 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726268

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60384

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.093	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	N
PhyloP100		-0.51
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.069
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.046	D
Polyphen		0.47	P
Vest4		0.27
MutPred		0.50		Loss of catalytic residue at T265 (P = 0.0489)
MVP		0.30
MPC		0.27
ClinPred		0.31	T
GERP RS		3.1
Varity_R		0.13
gMVP		0.017
Mutation Taster		=100/0	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: rs146940643; hg19: chr8-125989304;