chr4-145849505-C-T

Position:

• chr4-145849505-C-T

Variant summary

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

The NM_001306215.2(ZNF827):​c.2038G>A​(p.Asp680Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF827 NM_001306215.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20

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]

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
ZNF827	NM_001306215.2	c.2038G>A	p.Asp680Asn	missense_variant	6/15	ENST00000508784.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF827	ENST00000508784.6	c.2038G>A	p.Asp680Asn	missense_variant	6/15	1	NM_001306215.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251470 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135910

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Oct 14, 2023

The c.2038G>A (p.D680N) alteration is located in exon 6 (coding exon 6) of the ZNF827 gene. This alteration results from a G to A substitution at nucleotide position 2038, causing the aspartic acid (D) at amino acid position 680 to be replaced by an asparagine (N). 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	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.52
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.042	T;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	2.0	M;.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.81	N;N;N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.66
MutPred		0.18		Gain of glycosylation at S684 (P = 0.0737);.;Gain of glycosylation at S684 (P = 0.0737);
MVP		0.18
MPC		1.4
ClinPred		0.73	D
GERP RS		5.8
Varity_R		0.31
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs757994158; hg19: chr4-146770657;