chr15-90360346-C-T

Variant names:

• chr15-90360346-C-T
• rs1567102251
• NM_001004309.3:c.515C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T172S) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004309.3. 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
	ZNF774	NM_001004309.3	MANE Select	c.515C>T	p.Thr172Ile	missense	Exon 4 of 4	NP_001004309.2	Q6NX45

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF774	ENST00000354377.8	TSL:1 MANE Select	c.515C>T	p.Thr172Ile	missense	Exon 4 of 4	ENSP00000346348.3	Q6NX45
	ZNF774	ENST00000379090.9	TSL:1	c.211+1389C>T		intron	N/A	ENSP00000368383.5	E7EQ77
	ZNF774	ENST00000558115.1	TSL:3	n.507C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.1
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
Mutation Taster		=99/1	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: rs1567102251; hg19: chr15-90903578;