chr1-248850752-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF692	NM_017865.4	c.1183G>C	p.Ala395Pro	missense_variant	Exon 11 of 12	ENST00000306601.9	NP_060335.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF692	ENST00000306601.9	c.1183G>C	p.Ala395Pro	missense_variant	Exon 11 of 12	1	NM_017865.4	ENSP00000305483.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.52	N;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		1.0	D;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-249144951;