chr15-56631589-A-G

Position:

• chr15-56631589-A-G

Variant summary

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

The ENST00000267807.12(ZNF280D):​c.2849T>C​(p.Val950Ala) 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: 33)
• Consequence: ZNF280D ENST00000267807.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0690

Genes affected

ZNF280D (HGNC:25953): (zinc finger protein 280D) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF280D (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=0.061798006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF280D	NM_017661.4	c.2849T>C	p.Val950Ala	missense_variant	22/22	ENST00000267807.12	NP_060131.2
ZNF280D	NM_001288588.2	c.2849T>C	p.Val950Ala	missense_variant	22/22		NP_001275517.1
ZNF280D	NM_001002843.3	c.2810T>C	p.Val937Ala	missense_variant	21/21		NP_001002843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF280D	ENST00000267807.12	c.2849T>C	p.Val950Ala	missense_variant	22/22	1	NM_017661.4	ENSP00000267807.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

May 17, 2023

The c.2849T>C (p.V950A) alteration is located in exon 22 (coding exon 20) of the ZNF280D gene. This alteration results from a T to C substitution at nucleotide position 2849, causing the valine (V) at amino acid position 950 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	Benign	0.089
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.4
DANN	Benign	0.97
DEOGEN2	Benign	0.044	.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	.;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.78	.;N
REVEL	Benign	0.081
Sift	Benign	0.074	.;T
Sift4G	Benign	0.15	T;T
Polyphen		0.0020	.;B
Vest4		0.030
MutPred		0.076		.;Loss of methylation at K945 (P = 0.1806);
MVP		0.24
MPC		0.0088
ClinPred		0.065	T
GERP RS		1.9
Varity_R		0.024
gMVP		0.049

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: chr15-56923787;