rs763714116

Variant names:

• chr1-247100651-C-A
• rs763714116
• NM_001142572.2:c.860G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-247100651-C-A
• chr1-247100651-C-G
• chr1-247100651-C-T

Variant summary

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

The NM_001142572.2(ZNF669):​c.860G>T​(p.Arg287Leu) 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. 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. R287H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF669 NM_001142572.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

Genes affected

ZNF669 (HGNC:25736): (zinc finger protein 669) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be 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=0.08689791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF669	NM_001142572.2	c.860G>T	p.Arg287Leu	missense_variant	Exon 4 of 4	ENST00000448299.7	NP_001136044.1
ZNF669	NM_024804.3	c.1118G>T	p.Arg373Leu	missense_variant	Exon 4 of 4		NP_079080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF669	ENST00000448299.7	c.860G>T	p.Arg287Leu	missense_variant	Exon 4 of 4	1	NM_001142572.2	ENSP00000404370.2
ZNF669	ENST00000343381.10	c.1118G>T	p.Arg373Leu	missense_variant	Exon 4 of 4	1		ENSP00000342818.6
ZNF669	ENST00000366501.1	c.*670G>T		downstream_gene_variant		3		ENSP00000355457.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.42
DEOGEN2	Benign	0.00098	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.074	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.96	.;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.21	N;N
REVEL	Benign	0.074
Sift	Benign	0.64	T;T
Sift4G	Benign	0.64	T;T
Polyphen		0.80	.;P
Vest4		0.098
MutPred		0.63		.;Loss of MoRF binding (P = 0.0141);
MVP		0.040
MPC		0.087
ClinPred		0.086	T
GERP RS		-0.58
Varity_R		0.027
gMVP		0.047

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

LitVar

Other links and lift over

dbSNP: rs763714116; hg19: chr1-247263953;