chr5-16463256-C-A

Variant names:

• chr5-16463256-C-A
• rs201442736
• NM_033414.3:c.901G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033414.3(ZNF622):​c.901G>T​(p.Val301Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,596,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00031 (0 hom.)
• Consequence: ZNF622 NM_033414.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20154074).

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.901G>T	p.Val301Phe	missense	Exon 3 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.901G>T	p.Val301Phe	missense	Exon 3 of 6	ENSP00000310042.2	Q969S3
	ZNF622	ENST00000933612.1		c.901G>T	p.Val301Phe	missense	Exon 3 of 6	ENSP00000603671.1
	ZNF622	ENST00000933614.1		c.898G>T	p.Val300Phe	missense	Exon 3 of 6	ENSP00000603673.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000154 AC: 36 AN: 234212 AF XY: 0.000150

Gnomad AFR exome AF: 0.0000626

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000293

Gnomad OTH exome AF: 0.000526

GnomAD4 exome AF: 0.000310 AC: 448 AN: 1444824 Hom.: 0 Cov.: 31 AF XY: 0.000295 AC XY: 212 AN XY: 718028

African (AFR) AF: 0.00 AC: 0 AN: 32280

American (AMR) AF: 0.0000507 AC: 2 AN: 39474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25196

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 81582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.000397 AC: 440 AN: 1107984

Other (OTH) AF: 0.000100 AC: 6 AN: 59718

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152168 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74322

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000342 Hom.: 0

Bravo AF: 0.000128

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000123 AC: 15

EpiCase AF: 0.000164

EpiControl AF: 0.000237

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	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.030
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Benign	0.27	T
Sift4G	Benign	0.099	T
Polyphen		0.17	B
Vest4		0.46
MVP		0.41
MPC		1.1
ClinPred		0.13	T
GERP RS		5.0
Varity_R		0.18
gMVP		0.64
Mutation Taster		=89/11	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: rs201442736; hg19: chr5-16463365;