NM_017865.4:c.1183G>C

Variant names:

• chr1-248850752-C-G
• rs751034714
• NM_017865.4:c.1183G>C

Variant summary

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

The NM_017865.4(ZNF692):​c.1183G>C​(p.Ala395Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A395T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF692 NM_017865.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.47
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1183G>C	p.Ala395Pro	missense	Exon 11 of 12	NP_060335.2
	ZNF692	NM_001136036.3		c.1198G>C	p.Ala400Pro	missense	Exon 11 of 12	NP_001129508.1	Q9BU19-5
	ZNF692	NM_001350072.2		c.1180G>C	p.Ala394Pro	missense	Exon 11 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.1183G>C	p.Ala395Pro	missense	Exon 11 of 12	ENSP00000305483.5	Q9BU19-1
	ZNF692	ENST00000366471.7	TSL:1	c.1048G>C	p.Ala350Pro	missense	Exon 10 of 11	ENSP00000355427.3	Q9BU19-2
	ZNF692	ENST00000463519.5	TSL:1	n.*1428G>C		non_coding_transcript_exon	Exon 9 of 10	ENSP00000436308.1	Q9BU19-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.52	N
PhyloP100		5.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.69		Gain of disorder (P = 0.0599)
MVP		0.067
MPC		0.85
ClinPred		0.95	D
GERP RS		4.4
Varity_R		0.67
gMVP		0.50
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs751034714; hg19: chr1-249144951;