NM_152625.3:c.1738G>C

Variant names:

• chr5-72444253-C-G
• rs748360938
• NM_152625.3:c.1738G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152625.3(ZNF366):​c.1738G>C​(p.Gly580Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G580S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF366 NM_152625.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

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]

ENSG00000296791 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21435949).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152625.3. 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
	ZNF366	NM_152625.3	MANE Select	c.1738G>C	p.Gly580Arg	missense	Exon 5 of 5	NP_689838.1	Q8N895

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF366	ENST00000318442.6	TSL:1 MANE Select	c.1738G>C	p.Gly580Arg	missense	Exon 5 of 5	ENSP00000313158.5	Q8N895
	ZNF366	ENST00000867840.1		c.1738G>C	p.Gly580Arg	missense	Exon 6 of 6	ENSP00000537899.1
	ZNF366	ENST00000964997.1		c.1546G>C	p.Gly516Arg	missense	Exon 4 of 4	ENSP00000635056.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460982 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726798

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111880

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.062
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.15
Sift	Benign	0.064	T
Sift4G	Benign	0.38	T
Polyphen		0.97	D
Vest4		0.27
MutPred		0.33		Gain of MoRF binding (P = 0.0196)
MVP		0.12
MPC		0.13
ClinPred		0.69	D
GERP RS		5.9
Varity_R		0.099
gMVP		0.54
Mutation Taster		=95/5	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: rs748360938; hg19: chr5-71740080;