19-40074916-G-A

Position:

• chr19-40074916-G-A

Variant summary

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

The NM_001142578.2(ZNF780A):​c.1526C>T​(p.Ala509Val) 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. 12/21 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: ZNF780A NM_001142578.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.204

Genes affected

ZNF780A (HGNC:27603): (zinc finger protein 780A) 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. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09214547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF780A	NM_001142578.2	c.1526C>T	p.Ala509Val	missense_variant	6/6	ENST00000683561.1	NP_001136050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF780A	ENST00000683561.1	c.1526C>T	p.Ala509Val	missense_variant	6/6		NM_001142578.2	ENSP00000506741	A2

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

Feb 10, 2023

The c.1529C>T (p.A510V) alteration is located in exon 6 (coding exon 4) of the ZNF780A gene. This alteration results from a C to T substitution at nucleotide position 1529, causing the alanine (A) at amino acid position 510 to be replaced by a valine (V). 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	0.48
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	.;T;.;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.022	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.092	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.17	.;N;.;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.4	.;D;D;.;.
REVEL	Benign	0.045
Sift	Benign	0.042	.;D;D;.;.
Sift4G	Uncertain	0.022	D;D;D;D;D
Polyphen		0.38	.;B;.;B;.
Vest4		0.053
MutPred		0.58		.;Loss of disorder (P = 0.1059);.;Loss of disorder (P = 0.1059);.;
MVP		0.17
MPC		0.23
ClinPred		0.25	T
GERP RS		-0.42
Varity_R		0.098
gMVP		0.0090

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: chr19-40580823;