16-4752887-G-A

Position:

• chr16-4752887-G-A

Variant summary

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

The NM_021646.4(ZNF500):​c.932C>T​(p.Pro311Leu) 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: 34)
• Consequence: ZNF500 NM_021646.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.637

Genes affected

ZNF500 (HGNC:23716): (zinc finger protein 500) 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. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF500 (HGNC:):

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=0.062445372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF500	NM_021646.4	c.932C>T	p.Pro311Leu	missense_variant	6/6	ENST00000219478.11	NP_067678.1
ZNF500	NM_001303450.2	c.932C>T	p.Pro311Leu	missense_variant	6/7		NP_001290379.1
ZNF500	XM_011522453.3	c.932C>T	p.Pro311Leu	missense_variant	6/7		XP_011520755.1
ZNF500	XM_005255243.5	c.581C>T	p.Pro194Leu	missense_variant	5/5		XP_005255300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF500	ENST00000219478.11	c.932C>T	p.Pro311Leu	missense_variant	6/6	2	NM_021646.4	ENSP00000219478.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

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 25, 2024

The c.932C>T (p.P311L) alteration is located in exon 6 (coding exon 5) of the ZNF500 gene. This alteration results from a C to T substitution at nucleotide position 932, causing the proline (P) at amino acid position 311 to be replaced by a leucine (L). 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	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.89
DEOGEN2	Benign	0.022	T;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.27	T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.55	N;N;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N;N;.
REVEL	Benign	0.012
Sift	Benign	0.15	T;D;.
Sift4G	Benign	0.36	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.20
MutPred		0.33		Loss of glycosylation at P311 (P = 0.0215);Loss of glycosylation at P311 (P = 0.0215);.;
MVP		0.088
MPC		0.25
ClinPred		0.054	T
GERP RS		1.8
Varity_R		0.029
gMVP		0.089

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: chr16-4802888;