19-2853233-C-G

Position:

• chr19-2853233-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000334241.9(ZNF555):​c.1168C>G​(p.His390Asp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF555 ENST00000334241.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF555	NM_152791.5	c.1168C>G	p.His390Asp	missense_variant	4/4	ENST00000334241.9	NP_690004.4
ZNF555	NM_001172775.2	c.1165C>G	p.His389Asp	missense_variant	4/4		NP_001166246.1
ZNF555	XM_011527716.3	c.1174C>G	p.His392Asp	missense_variant	4/4		XP_011526018.1
ZNF555	XM_017026375.2	c.1171C>G	p.His391Asp	missense_variant	4/4		XP_016881864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF555	ENST00000334241.9	c.1168C>G	p.His390Asp	missense_variant	4/4	1	NM_152791.5	ENSP00000334853	P4
	ENST00000589365.1	n.397+5087G>C		intron_variant, non_coding_transcript_variant		4
ZNF555	ENST00000591539.1	c.1165C>G	p.His389Asp	missense_variant	4/4	2		ENSP00000467893	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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

Oct 25, 2022

The c.1168C>G (p.H390D) alteration is located in exon 4 (coding exon 4) of the ZNF555 gene. This alteration results from a C to G substitution at nucleotide position 1168, causing the histidine (H) at amino acid position 390 to be replaced by an aspartic acid (D). 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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Pathogenic	3.6	H;.
MutationTaster	Benign	0.79	D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-8.2	D;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.41
MutPred		0.76		Loss of MoRF binding (P = 0.0989);.;
MVP		0.75
MPC		0.34
ClinPred		1.0	D
GERP RS		3.2
Varity_R		0.80
gMVP		0.32

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: chr19-2853231;