19-57473369-C-G

Variant names:

• chr19-57473369-C-G
• NM_001144068.2:c.1252G>C

Variant summary

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

The NM_001144068.2(ZNF772):​c.1252G>C​(p.Glu418Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF772 NM_001144068.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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

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=0.22551283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF772	NM_001144068.2	c.1252G>C	p.Glu418Gln	missense_variant	Exon 4 of 4	ENST00000356584.8	NP_001137540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF772	ENST00000356584.8	c.1252G>C	p.Glu418Gln	missense_variant	Exon 4 of 4	2	NM_001144068.2	ENSP00000348992.3
ENSG00000268163	ENST00000596831.1	c.199+2291G>C		intron_variant	Intron 3 of 5	2		ENSP00000470969.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1375G>C (p.E459Q) alteration is located in exon 5 (coding exon 5) of the ZNF772 gene. This alteration results from a G to C substitution at nucleotide position 1375, causing the glutamic acid (E) at amino acid position 459 to be replaced by a glutamine (Q). 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.;.;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.53	T;T;T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L;.;.;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.7	D;D;N;.;.
REVEL	Benign	0.10
Sift	Benign	0.038	D;T;D;.;.
Sift4G	Uncertain	0.050	T;T;T;D;T
Polyphen		0.99	D;D;.;.;.
Vest4		0.15
MutPred		0.49		Gain of MoRF binding (P = 0.0321);.;.;.;.;
MVP		0.45
MPC		0.80
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.33
gMVP		0.085

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: chr19-57984737;