19-2850609-T-C

Position:

• chr19-2850609-T-C

Variant summary

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

The ENST00000334241.9(ZNF555):​c.26T>C​(p.Val9Ala) variant causes a missense change. 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: 32)
• Consequence: ZNF555 ENST00000334241.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

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, 0.791

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF555	NM_152791.5	c.26T>C	p.Val9Ala	missense_variant	2/4	ENST00000334241.9	NP_690004.4
ZNF555	NM_001172775.2	c.26T>C	p.Val9Ala	missense_variant	2/4		NP_001166246.1
ZNF555	XM_011527716.3	c.32T>C	p.Val11Ala	missense_variant	2/4		XP_011526018.1
ZNF555	XM_017026375.2	c.32T>C	p.Val11Ala	missense_variant	2/4		XP_016881864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF555	ENST00000334241.9	c.26T>C	p.Val9Ala	missense_variant	2/4	1	NM_152791.5	ENSP00000334853	P4
	ENST00000589365.1	n.398-3225A>G		intron_variant, non_coding_transcript_variant		4
ZNF555	ENST00000591539.1	c.26T>C	p.Val9Ala	missense_variant	2/4	2		ENSP00000467893	A2
ZNF555	ENST00000585966.5	c.-71T>C		5_prime_UTR_variant	2/4	4		ENSP00000466982

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

May 30, 2024

The c.26T>C (p.V9A) alteration is located in exon 2 (coding exon 2) of the ZNF555 gene. This alteration results from a T to C substitution at nucleotide position 26, causing the valine (V) at amino acid position 9 to be replaced by an alanine (A). 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	0.69
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0066	T
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	4.2	H;H
MutationTaster	Benign	0.98	N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.65
MutPred		0.74		Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.28
MPC		0.32
ClinPred		1.0	D
GERP RS		2.6
Varity_R		0.47
gMVP		0.16

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: chr19-2850607;