chr19-43997352-C-A

Variant names:

• chr19-43997352-C-A
• rs752705382
• NM_198089.3:c.1495C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198089.3(ZNF155):​c.1495C>A​(p.Arg499Ser) 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. 16/22 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. R499C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF155 NM_198089.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 1 publications found

Genes affected

ZNF155 (HGNC:12940): (zinc finger protein 155) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF230-DT (HGNC:55316): (ZNF230 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11073941).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198089.3. 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
	ZNF155	NM_198089.3	MANE Select	c.1495C>A	p.Arg499Ser	missense	Exon 5 of 5	NP_932355.3	Q12901-1
	ZNF155	NM_001260488.2		c.1528C>A	p.Arg510Ser	missense	Exon 6 of 6	NP_001247417.2	Q12901-2
	ZNF155	NM_001260486.2		c.1495C>A	p.Arg499Ser	missense	Exon 5 of 5	NP_001247415.2	Q12901-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF155	ENST00000270014.7	TSL:1 MANE Select	c.1495C>A	p.Arg499Ser	missense	Exon 5 of 5	ENSP00000270014.1	Q12901-1
	ZNF155	ENST00000590615.5	TSL:1	c.1495C>A	p.Arg499Ser	missense	Exon 5 of 5	ENSP00000465691.1	Q12901-1
	ZNF155	ENST00000407951.6	TSL:2	c.1528C>A	p.Arg510Ser	missense	Exon 6 of 6	ENSP00000385163.2	Q12901-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 79

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.00094	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.39
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.056
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.16	B
Vest4		0.15
MutPred		0.47		Gain of ubiquitination at K500 (P = 0.0239)
MVP		0.32
MPC		0.062
ClinPred		0.28	T
GERP RS		2.9
Varity_R		0.17
gMVP		0.074
Mutation Taster		=96/4	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: rs752705382; hg19: chr19-44501504; COSMIC: COSV108795866; COSMIC: COSV108795866;