chr19-43991926-G-A

Position:

• chr19-43991926-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198089.3(ZNF155):​c.227G>A​(p.Gly76Glu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF155 NM_198089.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0670

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07399726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF155	NM_198089.3	c.227G>A	p.Gly76Glu	missense_variant	4/5	ENST00000270014.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF155	ENST00000270014.7	c.227G>A	p.Gly76Glu	missense_variant	4/5	1	NM_198089.3	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Nov 18, 2022

The c.227G>A (p.G76E) alteration is located in exon 4 (coding exon 3) of the ZNF155 gene. This alteration results from a G to A substitution at nucleotide position 227, causing the glycine (G) at amino acid position 76 to be replaced by a glutamic acid (E). 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	0.089
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	.;T;.;.;T;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.11	T;T;T;T;.;.;T
M_CAP	Benign	0.00031	T
MetaRNN	Benign	0.074	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L;.;.;L;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.1	.;.;.;N;N;.;.
REVEL	Benign	0.058
Sift	Benign	0.15	.;.;.;T;T;.;.
Sift4G	Benign	0.50	T;T;T;T;T;T;T
Polyphen		0.54	.;P;.;.;P;P;.
Vest4		0.16, 0.17, 0.15, 0.15
MutPred		0.35		Loss of catalytic residue at G76 (P = 0.0242);Loss of catalytic residue at G76 (P = 0.0242);Loss of catalytic residue at G76 (P = 0.0242);.;Loss of catalytic residue at G76 (P = 0.0242);Loss of catalytic residue at G76 (P = 0.0242);Loss of catalytic residue at G76 (P = 0.0242);
MVP		0.27
MPC		0.061
ClinPred		0.11	T
GERP RS		0.43
Varity_R		0.085
gMVP		0.017

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-44496078;