NM_001322917.1:c.503C>T

Variant names:

• chr19-36719227-C-T
• NM_001322917.1:c.503C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001322917.1(ZNF567):​c.503C>T​(p.Ser168Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF567 NM_001322917.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.166
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04055196).

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.503C>T	p.Ser168Leu	missense	Exon 6 of 6	NP_001309846.1	Q8N184-3
	ZNF567	NM_001387759.1		c.572C>T	p.Ser191Leu	missense	Exon 7 of 7	NP_001374688.1
	ZNF567	NM_001300979.2		c.503C>T	p.Ser168Leu	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.503C>T	p.Ser168Leu	missense	Exon 6 of 6	ENSP00000507048.1	Q8N184-3
	ZNF567	ENST00000360729.8	TSL:1	c.410C>T	p.Ser137Leu	missense	Exon 4 of 4	ENSP00000353957.3	Q8N184-1
	ZNF567	ENST00000585696.5	TSL:1	c.410C>T	p.Ser137Leu	missense	Exon 3 of 3	ENSP00000467379.1	Q8N184-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.86
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.00047	N
LIST_S2	Benign	0.064	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.17
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.029
Sift	Benign	0.81	T
Sift4G	Benign	0.72	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.32		Loss of disorder (P = 0.014)
MVP		0.25
MPC		0.24
ClinPred		0.037	T
GERP RS		3.5
Varity_R		0.096
gMVP		0.090
Mutation Taster		=91/9	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

hg19: chr19-37210129; COSMIC: COSV62446142;