19-36719227-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF567	NM_001322917.1	c.503C>T	p.Ser168Leu	missense_variant	Exon 6 of 6	ENST00000682579.1	NP_001309846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF567	ENST00000682579.1	c.503C>T	p.Ser168Leu	missense_variant	Exon 6 of 6		NM_001322917.1	ENSP00000507048.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.410C>T (p.S137L) alteration is located in exon 4 (coding exon 3) of the ZNF567 gene. This alteration results from a C to T substitution at nucleotide position 410, causing the serine (S) at amino acid position 137 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.041	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.97	L;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.96	N;N;.;.
REVEL	Benign	0.029
Sift	Benign	0.81	T;T;.;.
Sift4G	Benign	0.72	T;T;T;T
Polyphen		0.0010	B;.;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-37210129; COSMIC: COSV62446142;