chr1-248855867-C-T

Variant names:

• chr1-248855867-C-T
• NM_017865.4:c.739G>A

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.739G>A​(p.Ala247Thr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF692 NM_017865.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.570
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.075847834).

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.739G>A	p.Ala247Thr	missense	Exon 7 of 12	NP_060335.2
	ZNF692	NM_001136036.3		c.754G>A	p.Ala252Thr	missense	Exon 7 of 12	NP_001129508.1	Q9BU19-5
	ZNF692	NM_001350072.2		c.736G>A	p.Ala246Thr	missense	Exon 7 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.739G>A	p.Ala247Thr	missense	Exon 7 of 12	ENSP00000305483.5	Q9BU19-1
	ZNF692	ENST00000366471.7	TSL:1	c.604G>A	p.Ala202Thr	missense	Exon 6 of 11	ENSP00000355427.3	Q9BU19-2
	ZNF692	ENST00000463519.5	TSL:1	n.*984G>A		non_coding_transcript_exon	Exon 5 of 10	ENSP00000436308.1	Q9BU19-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.57
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.050
Sift	Uncertain	0.012	D
Sift4G	Benign	0.53	T
Polyphen		0.16	B
Vest4		0.063
MutPred		0.21		Gain of glycosylation at A247 (P = 0.0016)
MVP		0.014
MPC		0.18
ClinPred		0.11	T
GERP RS		3.1
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.12
Mutation Taster		=95/5	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

hg19: chr1-249150066;