19-57473517-G-C

Position:

• chr19-57473517-G-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.1104C>G​(p.Ile368Met) 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. 13/21 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: ZNF772 NM_001144068.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -6.21

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=0.09965351).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF772	NM_001144068.2	c.1104C>G	p.Ile368Met	missense_variant	4/4	ENST00000356584.8	NP_001137540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF772	ENST00000356584.8	c.1104C>G	p.Ile368Met	missense_variant	4/4	2	NM_001144068.2	ENSP00000348992.3
ENSG00000268163	ENST00000596831.1	c.199+2143C>G		intron_variant		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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.1227C>G (p.I409M) alteration is located in exon 5 (coding exon 5) of the ZNF772 gene. This alteration results from a C to G substitution at nucleotide position 1227, causing the isoleucine (I) at amino acid position 409 to be replaced by a methionine (M). 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	Benign	0.095
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0070	T;.;.;.;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.072	T;T;T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N;.;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.34	N;N;N;.;.
REVEL	Benign	0.070
Sift	Benign	0.042	D;T;T;.;.
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		1.0	D;B;.;.;.
Vest4		0.17
MutPred		0.33		Gain of ubiquitination at K413 (P = 0.0828);.;.;.;.;
MVP		0.26
MPC		0.81
ClinPred		0.11	T
GERP RS		1.3
Varity_R		0.053
gMVP		0.081

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: chr19-57984885; COSMIC: COSV105911857; COSMIC: COSV105911857;