5-72444186-G-T

Variant names:

• chr5-72444186-G-T
• rs576990982
• NM_152625.3:c.1805C>A

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.1805C>A​(p.Pro602Gln) 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 1,461,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P602L) 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: 3.46
• 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=0.1567364).

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.1805C>A	p.Pro602Gln	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.1805C>A	p.Pro602Gln	missense	Exon 5 of 5	ENSP00000313158.5	Q8N895
	ZNF366	ENST00000867840.1		c.1805C>A	p.Pro602Gln	missense	Exon 6 of 6	ENSP00000537899.1
	ZNF366	ENST00000964997.1		c.1613C>A	p.Pro538Gln	missense	Exon 4 of 4	ENSP00000635056.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461168 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726902

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.5
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.069
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.058	T
Polyphen		0.80	P
Vest4		0.17
MutPred		0.25		Gain of helix (P = 0.0128)
MVP		0.18
MPC		0.041
ClinPred		0.70	D
GERP RS		5.6
Varity_R		0.033
gMVP		0.31
Mutation Taster		=92/8	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: rs576990982; hg19: chr5-71740013;