19-40034692-T-C

Position:

• chr19-40034692-T-C

Variant summary

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

The NM_001005851.3(ZNF780B):​c.2167A>G​(p.Lys723Glu) 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: ZNF780B NM_001005851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.78

Genes affected

ZNF780B (HGNC:33109): (zinc finger protein 780B) Predicted to enable DNA-binding transcription activator 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=0.24972293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF780B	NM_001005851.3	c.2167A>G	p.Lys723Glu	missense_variant	5/5	ENST00000434248.6	NP_001005851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF780B	ENST00000434248.6	c.2167A>G	p.Lys723Glu	missense_variant	5/5	5	NM_001005851.3	ENSP00000391641	P1
ZNF780B	ENST00000221355.10	c.1723A>G	p.Lys575Glu	missense_variant	6/6	2		ENSP00000221355

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jan 24, 2024

The c.2167A>G (p.K723E) alteration is located in exon 5 (coding exon 4) of the ZNF780B gene. This alteration results from a A to G substitution at nucleotide position 2167, causing the lysine (K) at amino acid position 723 to be replaced by a glutamic acid (E). 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	0.55
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.028	N
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;.
MutationTaster	Benign	0.94	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.8	.;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.019	.;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.19
MutPred		0.54		Loss of methylation at K723 (P = 0.002);Loss of methylation at K723 (P = 0.002);.;
MVP		0.48
MPC		0.34
ClinPred		0.96	D
GERP RS		2.4
Varity_R		0.35
gMVP		0.0089

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: chr19-40540599;