19-43997352-C-T

Variant names:

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

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>T​(p.Arg499Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R499G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ZNF155 NM_198089.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.115713716).

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>T	p.Arg499Cys	missense	Exon 5 of 5	NP_932355.3	Q12901-1
	ZNF155	NM_001260488.2		c.1528C>T	p.Arg510Cys	missense	Exon 6 of 6	NP_001247417.2	Q12901-2
	ZNF155	NM_001260486.2		c.1495C>T	p.Arg499Cys	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>T	p.Arg499Cys	missense	Exon 5 of 5	ENSP00000270014.1	Q12901-1
	ZNF155	ENST00000590615.5	TSL:1	c.1495C>T	p.Arg499Cys	missense	Exon 5 of 5	ENSP00000465691.1	Q12901-1
	ZNF155	ENST00000407951.6	TSL:2	c.1528C>T	p.Arg510Cys	missense	Exon 6 of 6	ENSP00000385163.2	Q12901-2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151982 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000278 AC: 7 AN: 251364 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461532 Hom.: 0 Cov.: 79 AF XY: 0.0000206 AC XY: 15 AN XY: 727064

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.0000224 AC: 1 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39690

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111760

Other (OTH) AF: 0.0000497 AC: 3 AN: 60388

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152100 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000205 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Benign	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.00095	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		0.39
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.78	N
REVEL	Benign	0.093
Sift	Benign	0.060	T
Sift4G	Uncertain	0.043	D
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.55		Loss of MoRF binding (P = 0.0081)
MVP		0.31
MPC		0.039
ClinPred		0.056	T
GERP RS		2.9
Varity_R		0.10
gMVP		0.049
Mutation Taster		=97/3	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;