19-53164724-T-A

Variant names:

• chr19-53164724-T-A
• rs1568651544
• NM_024733.5:c.1766A>T

Variant summary

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

The NM_024733.5(ZNF665):​c.1766A>T​(p.Gln589Leu) 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. 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. Q589R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF665 NM_024733.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429
• Publications: 0 publications found

Genes affected

ZNF665 (HGNC:25885): (zinc finger protein 665) 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: 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=0.087887645).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024733.5. 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
	ZNF665	NM_024733.5	MANE Select	c.1766A>T	p.Gln589Leu	missense	Exon 4 of 4	NP_079009.3
	ZNF665	NM_001353458.2		c.1850A>T	p.Gln617Leu	missense	Exon 5 of 5	NP_001340387.1
	ZNF665	NM_001353459.2		c.1766A>T	p.Gln589Leu	missense	Exon 4 of 4	NP_001340388.1	Q9H7R5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF665	ENST00000396424.5	TSL:2 MANE Select	c.1766A>T	p.Gln589Leu	missense	Exon 4 of 4	ENSP00000379702.2	Q9H7R5
	ZNF665	ENST00000650736.1		c.1766A>T	p.Gln589Leu	missense	Exon 5 of 5	ENSP00000498600.1	Q9H7R5
	ZNF665	ENST00000868912.1		c.1766A>T	p.Gln589Leu	missense	Exon 4 of 4	ENSP00000538971.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 80

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N
PhyloP100		0.43
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.048
Sift	Benign	0.079	T
Sift4G	Uncertain	0.043	D
Polyphen		0.86	P
Vest4		0.20
MutPred		0.43		Loss of catalytic residue at Q589 (P = 0.0368)
MVP		0.29
MPC		0.032
ClinPred		0.29	T
GERP RS		0.28
Varity_R		0.20
gMVP		0.079
Mutation Taster		=100/0	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: rs1568651544; hg19: chr19-53667977;