rs746919093

Variant names:

• chr5-16463629-C-G
• rs746919093
• NM_033414.3:c.739G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-16463629-C-G
• chr5-16463629-C-T

Variant summary

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

The NM_033414.3(ZNF622):​c.739G>C​(p.Gly247Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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. G247S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF622 NM_033414.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.35
• Publications: 0 publications found

Genes affected

ZNF622 (HGNC:30958): (zinc finger protein 622) Enables RNA binding activity. Involved in several processes, including intrinsic apoptotic signaling pathway in response to oxidative stress; positive regulation of JNK cascade; and positive regulation of kinase activity. Located in Golgi apparatus; cytosol; and nuclear lumen. [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_033414.3. 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
	ZNF622	NM_033414.3	MANE Select	c.739G>C	p.Gly247Arg	missense	Exon 2 of 6	NP_219482.1	Q969S3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF622	ENST00000308683.3	TSL:1 MANE Select	c.739G>C	p.Gly247Arg	missense	Exon 2 of 6	ENSP00000310042.2	Q969S3
	ZNF622	ENST00000933612.1		c.739G>C	p.Gly247Arg	missense	Exon 2 of 6	ENSP00000603671.1
	ZNF622	ENST00000933614.1		c.739G>C	p.Gly247Arg	missense	Exon 2 of 6	ENSP00000603673.1

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	0.33
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.31		Gain of solvent accessibility (P = 0.0584)
MVP		0.53
MPC		1.2
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.45
gMVP		0.34
Mutation Taster		=71/29	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: rs746919093; hg19: chr5-16463738;