19-2851483-T-G

Position:

• chr19-2851483-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000334241.9(ZNF555):​c.146T>G​(p.Phe49Cys) 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: ZNF555 ENST00000334241.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.21

Genes affected

ZNF555 (HGNC:28382): (zinc finger protein 555) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

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=0.049172103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF555	NM_152791.5	c.146T>G	p.Phe49Cys	missense_variant	3/4	ENST00000334241.9	NP_690004.4
ZNF555	NM_001172775.2	c.146T>G	p.Phe49Cys	missense_variant	3/4		NP_001166246.1
ZNF555	XM_011527716.3	c.152T>G	p.Phe51Cys	missense_variant	3/4		XP_011526018.1
ZNF555	XM_017026375.2	c.152T>G	p.Phe51Cys	missense_variant	3/4		XP_016881864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF555	ENST00000334241.9	c.146T>G	p.Phe49Cys	missense_variant	3/4	1	NM_152791.5	ENSP00000334853	P4
	ENST00000589365.1	n.398-4099A>C		intron_variant, non_coding_transcript_variant		4
ZNF555	ENST00000591539.1	c.146T>G	p.Phe49Cys	missense_variant	3/4	2		ENSP00000467893	A2
ZNF555	ENST00000585966.5	c.50T>G	p.Phe17Cys	missense_variant	3/4	4		ENSP00000466982

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.146T>G (p.F49C) alteration is located in exon 3 (coding exon 3) of the ZNF555 gene. This alteration results from a T to G substitution at nucleotide position 146, causing the phenylalanine (F) at amino acid position 49 to be replaced by a cysteine (C). 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	0.092
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.033	T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.16	T;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.049	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.27	N;.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.74	N;.;.
REVEL	Benign	0.013
Sift	Benign	0.21	T;.;.
Sift4G	Benign	0.17	T;D;T
Polyphen		0.0010	B;.;.
Vest4		0.22
MutPred		0.31		Loss of catalytic residue at F49 (P = 0.0258);.;Loss of catalytic residue at F49 (P = 0.0258);
MVP		0.15
MPC		0.054
ClinPred		0.039	T
GERP RS		-0.93
Varity_R		0.11
gMVP		0.054

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-2851481;