5-72444179-G-T

Position:

• chr5-72444179-G-T

Variant summary

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

The ENST00000318442.6(ZNF366):​c.1812C>A​(p.Phe604Leu) 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: ZNF366 ENST00000318442.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60

Genes affected

ZNF366 (HGNC:18316): (zinc finger protein 366) Enables estrogen receptor binding activity and transcription corepressor activity. Involved in negative regulation of intracellular estrogen receptor signaling pathway; negative regulation of transcription by RNA polymerase II; and response to estrogen. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13124886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF366	NM_152625.3	c.1812C>A	p.Phe604Leu	missense_variant	5/5	ENST00000318442.6	NP_689838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF366	ENST00000318442.6	c.1812C>A	p.Phe604Leu	missense_variant	5/5	1	NM_152625.3	ENSP00000313158	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Jan 03, 2024

The c.1812C>A (p.F604L) alteration is located in exon 5 (coding exon 4) of the ZNF366 gene. This alteration results from a C to A substitution at nucleotide position 1812, causing the phenylalanine (F) at amino acid position 604 to be replaced by a leucine (L). 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	Uncertain	0.53
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	0.95	D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.051
Sift	Benign	0.25	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.22
MutPred		0.35		Loss of catalytic residue at F604 (P = 0.0419);
MVP		0.19
MPC		0.022
ClinPred		0.15	T
GERP RS		1.7
Varity_R		0.071
gMVP		0.11

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: chr5-71740006;