NM_001142578.2:c.1537T>C

Variant names:

• chr19-40074905-A-G
• rs778053073
• NM_001142578.2:c.1537T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142578.2(ZNF780A):​c.1537T>C​(p.Tyr513His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZNF780A NM_001142578.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -7.11
• Publications: 0 publications found

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]

ENSG00000269749 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03862831).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142578.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF780A	NM_001142578.2	MANE Select	c.1537T>C	p.Tyr513His	missense	Exon 6 of 6	NP_001136050.1	O75290-1
	ZNF780A	NM_001142577.2		c.1540T>C	p.Tyr514His	missense	Exon 6 of 6	NP_001136049.1	O75290-3
	ZNF780A	NM_001010880.3		c.1537T>C	p.Tyr513His	missense	Exon 6 of 6	NP_001010880.2	O75290-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF780A	ENST00000683561.1	MANE Select	c.1537T>C	p.Tyr513His	missense	Exon 6 of 6	ENSP00000506741.1	O75290-1
	ZNF780A	ENST00000907466.1		c.1561T>C	p.Tyr521His	missense	Exon 6 of 6	ENSP00000577525.1
	ZNF780A	ENST00000455521.5	TSL:5	c.1540T>C	p.Tyr514His	missense	Exon 6 of 6	ENSP00000400997.1	O75290-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251344 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461872 Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.052
DANN	Benign	0.50
DEOGEN2	Benign	0.0023	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0073	N
M_CAP	Benign	0.00071	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.59	N
PhyloP100		-7.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.042
Sift	Benign	0.59	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.034
MVP		0.092
MPC		0.14
ClinPred		0.028	T
GERP RS		-3.9
Varity_R		0.020
gMVP		0.020
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs778053073; hg19: chr19-40580812;