19-2834236-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001102651.2(ZNF554):​c.1001A>C​(p.Asn334Thr) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N334I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF554 NM_001102651.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049766243).

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>C	p.Asn334Thr	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>C	p.Asn334Thr	missense	Exon 5 of 5	ENSP00000321132.4	Q86TJ5
	ZNF554	ENST00000901630.1		c.998A>C	p.Asn333Thr	missense	Exon 5 of 5	ENSP00000571689.1
	ZNF554	ENST00000963471.1		c.959A>C	p.Asn320Thr	missense	Exon 5 of 5	ENSP00000633530.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.000040	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.27	N
PhyloP100		-1.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.030
Sift	Benign	0.26	T
Sift4G	Benign	0.14	T
Polyphen		0.13	B
Vest4		0.085
MutPred		0.37		Gain of glycosylation at N334 (P = 0.0726)
MVP		0.16
MPC		0.62
ClinPred		0.18	T
GERP RS		1.6
Varity_R		0.080
gMVP		0.047
Mutation Taster		=99/1	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;