4-145765709-T-C

Variant summary

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

The NM_001306215.2(ZNF827):c.2890A>G(p.Asn964Asp) 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: 31)
• Consequence: ZNF827 NM_001306215.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.53

Genes affected

ZNF827 (HGNC:27193): (zinc finger protein 827) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

C4orf51 (HGNC:37264): (chromosome 4 open reading frame 51)

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=0.10401398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF827	NM_001306215.2	c.2890A>G	p.Asn964Asp	missense_variant	12/15	ENST00000508784.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF827	ENST00000508784.6	c.2890A>G	p.Asn964Asp	missense_variant	12/15	1	NM_001306215.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

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

Dec 27, 2023

The c.2890A>G (p.N964D) alteration is located in exon 12 (coding exon 12) of the ZNF827 gene. This alteration results from a A to G substitution at nucleotide position 2890, causing the asparagine (N) at amino acid position 964 to be replaced by an aspartic acid (D). 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	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.026	T;.;.
Eigen	Benign	-0.037
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;N
MutationTaster	Benign	0.54	D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.91	N;N;N
REVEL	Benign	0.057
Sift	Benign	0.094	T;T;T
Sift4G	Uncertain	0.0060	D;T;D
Polyphen		0.016	B;B;B
Vest4		0.26
MutPred		0.41		Gain of glycosylation at S967 (P = 0.0079);.;Gain of glycosylation at S967 (P = 0.0079);
MVP		0.043
MPC		0.57
ClinPred		0.62	D
GERP RS		5.6
Varity_R		0.096
gMVP		0.44

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: chr4-146686861;