19-57473600-C-G

Variant names:

• chr19-57473600-C-G
• rs142150770
• NM_001144068.2:c.1021G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144068.2(ZNF772):​c.1021G>C​(p.Glu341Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E341K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF772 NM_001144068.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 0 publications found

Genes affected

ZNF772 (HGNC:33106): (zinc finger protein 772) 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]

ENSG00000268163 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19888812).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144068.2. 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
	ZNF772	NM_001144068.2	MANE Select	c.1021G>C	p.Glu341Gln	missense	Exon 4 of 4	NP_001137540.1	Q68DY9-3
	ZNF772	NM_001024596.3		c.1144G>C	p.Glu382Gln	missense	Exon 5 of 5	NP_001019767.1	Q68DY9-1
	ZNF772	NM_001439216.1		c.982G>C	p.Glu328Gln	missense	Exon 3 of 3	NP_001426145.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF772	ENST00000356584.8	TSL:2 MANE Select	c.1021G>C	p.Glu341Gln	missense	Exon 4 of 4	ENSP00000348992.3	Q68DY9-3
	ZNF772	ENST00000343280.8	TSL:1	c.1144G>C	p.Glu382Gln	missense	Exon 5 of 5	ENSP00000341165.4	Q68DY9-1
	ZNF772	ENST00000427512.6	TSL:1	c.808G>C	p.Glu270Gln	missense	Exon 2 of 2	ENSP00000395967.2	Q68DY9-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 727224

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.033
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.35	N
PhyloP100		0.039
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.12
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.17
MutPred		0.52		Loss of ubiquitination at K385 (P = 0.0352)
MVP		0.46
MPC		0.80
ClinPred		0.83	D
GERP RS		4.1
Varity_R		0.27
gMVP		0.15
Mutation Taster		=96/4	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: rs142150770; hg19: chr19-57984968;