rs748360938

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-72444253-C-G
• chr5-72444253-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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=0.21435949).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF366	NM_152625.3	c.1738G>C	p.Gly580Arg	missense_variant	Exon 5 of 5	ENST00000318442.6	NP_689838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF366	ENST00000318442.6	c.1738G>C	p.Gly580Arg	missense_variant	Exon 5 of 5	1	NM_152625.3	ENSP00000313158.5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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: chr5-71740080;