15-90360346-C-T

Variant names:

• chr15-90360346-C-T
• NM_001004309.3:c.515C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004309.3(ZNF774):​c.515C>T​(p.Thr172Ile) 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF774 NM_001004309.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.06

Genes affected

ZNF774 (HGNC:33108): (zinc finger protein 774) 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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044674963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF774	NM_001004309.3	c.515C>T	p.Thr172Ile	missense_variant	Exon 4 of 4	ENST00000354377.8	NP_001004309.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF774	ENST00000354377.8	c.515C>T	p.Thr172Ile	missense_variant	Exon 4 of 4	1	NM_001004309.3	ENSP00000346348.3
ZNF774	ENST00000379090.9	c.211+1389C>T		intron_variant	Intron 3 of 4	1		ENSP00000368383.5
ZNF774	ENST00000558115.1	n.507C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
ZNF774	ENST00000560038.5	n.*446C>T		downstream_gene_variant		4		ENSP00000453202.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Feb 04, 2021

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

Gene of uncertain clinical significance -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.63
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.32	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.067
Sift	Benign	1.0	T
Sift4G	Benign	0.61	T
Polyphen		0.15	B
Vest4		0.096
MutPred		0.45		Loss of catalytic residue at T172 (P = 0.0383);
MVP		0.22
MPC		0.30
ClinPred		0.18	T
GERP RS		2.9
Varity_R		0.098
gMVP		0.072

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: chr15-90903578;