chr19-43996707-G-T

Position:

• chr19-43996707-G-T

Variant summary

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

The NM_198089.3(ZNF155):​c.850G>T​(p.Gly284Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF155 NM_198089.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF155	NM_198089.3	c.850G>T	p.Gly284Trp	missense_variant	5/5	ENST00000270014.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF155	ENST00000270014.7	c.850G>T	p.Gly284Trp	missense_variant	5/5	1	NM_198089.3	P2
ZNF155	ENST00000590615.5	c.850G>T	p.Gly284Trp	missense_variant	5/5	1		P2
ZNF155	ENST00000407951.6	c.883G>T	p.Gly295Trp	missense_variant	6/6	2		A2
ZNF155	ENST00000611002.4	c.850G>T	p.Gly284Trp	missense_variant	5/5	4		P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 77 AF XY: 0.00 AC XY: 0 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 15, 2023

The c.850G>T (p.G284W) alteration is located in exon 5 (coding exon 4) of the ZNF155 gene. This alteration results from a G to T substitution at nucleotide position 850, causing the glycine (G) at amino acid position 284 to be replaced by a tryptophan (W). 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	Pathogenic	0.90
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;.;T;T
Eigen	Uncertain	0.42
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T;T;.;.
M_CAP	Benign	0.0063	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.3	M;.;M;M
MutationTaster	Benign	0.76	D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-7.4	.;D;D;.
REVEL	Benign	0.20
Sift	Pathogenic	0.0	.;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.45
MutPred		0.48		Loss of disorder (P = 0.0062);.;Loss of disorder (P = 0.0062);Loss of disorder (P = 0.0062);
MVP		0.49
MPC		0.26
ClinPred		1.0	D
GERP RS		2.6
Varity_R		0.46
gMVP		0.020

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: chr19-44500859;