1-248850370-C-A

Variant names:

• chr1-248850370-C-A
• rs765351127
• NM_017865.4:c.1400G>T

Variant summary

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

The NM_017865.4(ZNF692):​c.1400G>T​(p.Arg467Leu) 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. R467C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF692 NM_017865.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 6 publications found

Genes affected

ZNF692 (HGNC:26049): (zinc finger protein 692) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II and regulation of gluconeogenesis. Located in nucleolus and nucleoplasm. [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=0.104177505).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017865.4. 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
	ZNF692	NM_017865.4	MANE Select	c.1400G>T	p.Arg467Leu	missense	Exon 12 of 12	NP_060335.2
	ZNF692	NM_001136036.3		c.1415G>T	p.Arg472Leu	missense	Exon 12 of 12	NP_001129508.1	Q9BU19-5
	ZNF692	NM_001350072.2		c.1397G>T	p.Arg466Leu	missense	Exon 12 of 12	NP_001337001.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF692	ENST00000306601.9	TSL:1 MANE Select	c.1400G>T	p.Arg467Leu	missense	Exon 12 of 12	ENSP00000305483.5	Q9BU19-1
	ZNF692	ENST00000366471.7	TSL:1	c.1265G>T	p.Arg422Leu	missense	Exon 11 of 11	ENSP00000355427.3	Q9BU19-2
	ZNF692	ENST00000463519.5	TSL:1	n.*1645G>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000436308.1	Q9BU19-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.3
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.11
Sift	Benign	0.11	T
Sift4G	Benign	0.075	T
Polyphen		0.014	B
Vest4		0.082
MutPred		0.48		Gain of ubiquitination at K469 (P = 0.042)
MVP		0.088
MPC		0.25
ClinPred		0.14	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.30
Mutation Taster		=76/24	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: rs765351127; hg19: chr1-249144569;