19-36719965-C-G

Variant names:

• chr19-36719965-C-G
• rs200779985
• NM_001322917.1:c.1241C>G

Variant summary

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

The NM_001322917.1(ZNF567):​c.1241C>G​(p.Thr414Ser) 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. 14/22 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. T414I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF567 NM_001322917.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 0 publications found

Genes affected

ZNF567 (HGNC:28696): (zinc finger protein 567) 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]

ZNF850 (HGNC:27994): (zinc finger protein 850) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific 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 active 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=0.2476342).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322917.1. 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
	ZNF567	NM_001322917.1	MANE Select	c.1241C>G	p.Thr414Ser	missense	Exon 6 of 6	NP_001309846.1	Q8N184-3
	ZNF567	NM_001387759.1		c.1310C>G	p.Thr437Ser	missense	Exon 7 of 7	NP_001374688.1
	ZNF567	NM_001300979.2		c.1241C>G	p.Thr414Ser	missense	Exon 6 of 6	NP_001287908.1	Q8N184-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF567	ENST00000682579.1	MANE Select	c.1241C>G	p.Thr414Ser	missense	Exon 6 of 6	ENSP00000507048.1	Q8N184-3
	ZNF567	ENST00000360729.8	TSL:1	c.1148C>G	p.Thr383Ser	missense	Exon 4 of 4	ENSP00000353957.3	Q8N184-1
	ZNF567	ENST00000585696.5	TSL:1	c.1148C>G	p.Thr383Ser	missense	Exon 3 of 3	ENSP00000467379.1	Q8N184-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.081	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.57
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.072
Sift	Benign	0.15	T
Sift4G	Benign	0.28	T
Polyphen		0.024	B
Vest4		0.22
MutPred		0.58		Gain of disorder (P = 0.106)
MVP		0.55
MPC		0.72
ClinPred		0.61	D
GERP RS		1.9
Varity_R		0.055
gMVP		0.047
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: rs200779985; hg19: chr19-37210867;