19-43996252-C-T

Position:

• chr19-43996252-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198089.3(ZNF155):​c.395C>T​(p.Ser132Phe) 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. 15/21 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: ZNF155 NM_198089.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.457

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06100616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF155	NM_198089.3	c.395C>T	p.Ser132Phe	missense_variant	5/5	ENST00000270014.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF155	ENST00000270014.7	c.395C>T	p.Ser132Phe	missense_variant	5/5	1	NM_198089.3	P2

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

Mar 20, 2023

The c.395C>T (p.S132F) alteration is located in exon 5 (coding exon 4) of the ZNF155 gene. This alteration results from a C to T substitution at nucleotide position 395, causing the serine (S) at amino acid position 132 to be replaced by a phenylalanine (F). 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	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.58
DANN	Benign	0.11
DEOGEN2	Benign	0.0045	T;.;.;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.47	T;T;T;.;.
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.061	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.76	N;.;.;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.4	.;.;N;N;.
REVEL	Benign	0.0090
Sift	Benign	0.24	.;.;T;T;.
Sift4G	Benign	0.69	T;T;T;T;T
Polyphen		0.0020	B;.;.;B;B
Vest4		0.17
MutPred		0.43		Gain of catalytic residue at S132 (P = 0.0031);Gain of catalytic residue at S132 (P = 0.0031);.;Gain of catalytic residue at S132 (P = 0.0031);Gain of catalytic residue at S132 (P = 0.0031);
MVP		0.061
MPC		0.035
ClinPred		0.035	T
GERP RS		-1.8
Varity_R		0.032
gMVP		0.031

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-44500404;