6-57147602-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031623.3(ZNF451):c.1517T>C(p.Val506Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF451 NM_001031623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.38

Genes affected

ZNF451 (HGNC:21091): (zinc finger protein 451) Enables SUMO ligase activity and transcription corepressor activity. Involved in negative regulation of nitrogen compound metabolic process; negative regulation of transforming growth factor beta receptor signaling pathway; and protein sumoylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF451-AS1 (HGNC:53824): (ZNF451 regulatory antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32009053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF451	NM_001031623.3	c.1517T>C	p.Val506Ala	missense_variant	10/15	ENST00000370706.9
ZNF451-AS1	NR_110742.1	n.234+23403A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF451	ENST00000370706.9	c.1517T>C	p.Val506Ala	missense_variant	10/15	1	NM_001031623.3	P2
ZNF451-AS1	ENST00000416069.6	n.443+23403A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 06, 2023

The c.1517T>C (p.V506A) alteration is located in exon 10 (coding exon 10) of the ZNF451 gene. This alteration results from a T to C substitution at nucleotide position 1517, causing the valine (V) at amino acid position 506 to be replaced by an alanine (A). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Uncertain	24
Dann	Uncertain	0.98
DEOGEN2	Benign	0.024	T;.;T
Eigen	Benign	0.076
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.0	L;L;.
MutationTaster	Benign	0.84	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.37	N;N;N
REVEL	Benign	0.064
Sift	Benign	0.12	T;T;T
Sift4G	Uncertain	0.053	T;T;T
Polyphen		0.92	P;P;P
Vest4		0.27
MutPred		0.44		Loss of methylation at K505 (P = 0.0408);Loss of methylation at K505 (P = 0.0408);Loss of methylation at K505 (P = 0.0408);
MVP		0.43
MPC		0.68
ClinPred		0.55	D
GERP RS		5.3
Varity_R		0.053
gMVP		0.19

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: chr6-57012400;