7-149474647-G-C

Position:

• chr7-149474647-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001394198.1(ZNF746):​c.1720C>G​(p.Arg574Gly) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF746 NM_001394198.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

Genes affected

ZNF746 (HGNC:21948): (zinc finger protein 746) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and ubiquitin protein ligase binding activity. Involved in negative regulation of transcription by RNA polymerase II; positive regulation of neuron death; and positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF746	NM_001394198.1	c.1720C>G	p.Arg574Gly	missense_variant	7/7	ENST00000458143.7	NP_001381127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF746	ENST00000458143.7	c.1720C>G	p.Arg574Gly	missense_variant	7/7	2	NM_001394198.1	ENSP00000395007.3
ZNF746	ENST00000340622.8	c.1672C>G	p.Arg558Gly	missense_variant	7/7	1		ENSP00000345140.3
ZNF746	ENST00000644635.1	c.1717C>G	p.Arg573Gly	missense_variant	7/7			ENSP00000493970.1
ZNF746	ENST00000685153.1	c.1675C>G	p.Arg559Gly	missense_variant	7/7			ENSP00000508891.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	.;T;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	.;M;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.0	.;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	.;D;D
Sift4G	Uncertain	0.0080	.;D;D
Polyphen		0.92, 1.0	.;P;D
Vest4		0.52, 0.51
MutPred		0.81		.;Loss of MoRF binding (P = 0.0713);.;
MVP		0.52
MPC		1.8
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.66
gMVP		0.83

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: chr7-149171738;