chr19-2834236-A-T

Variant names:

• chr19-2834236-A-T
• rs751719426
• NM_001102651.2:c.1001A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001102651.2(ZNF554):​c.1001A>T​(p.Asn334Ile) 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. 13/22 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: ZNF554 NM_001102651.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.52
• Publications: 0 publications found

Genes affected

ZNF554 (HGNC:26629): (zinc finger protein 554) 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. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29548454).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102651.2. 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
	ZNF554	NM_001102651.2	MANE Select	c.1001A>T	p.Asn334Ile	missense	Exon 5 of 5	NP_001096121.1	Q86TJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF554	ENST00000317243.10	TSL:1 MANE Select	c.1001A>T	p.Asn334Ile	missense	Exon 5 of 5	ENSP00000321132.4	Q86TJ5
	ZNF554	ENST00000901630.1		c.998A>T	p.Asn333Ile	missense	Exon 5 of 5	ENSP00000571689.1
	ZNF554	ENST00000963471.1		c.959A>T	p.Asn320Ile	missense	Exon 5 of 5	ENSP00000633530.1

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	Pathogenic	0.61
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.000030	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.050	N
PhyloP100		-1.5
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.062
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.035	D
Polyphen		0.99	D
Vest4		0.27
MutPred		0.53		Loss of disorder (P = 0.0272)
MVP		0.41
MPC		0.68
ClinPred		0.78	D
GERP RS		1.6
Varity_R		0.33
gMVP		0.083
Mutation Taster		=94/6	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

dbSNP: rs751719426; hg19: chr19-2834234;