Genetic Variant ZNF622:p.Asp377Asn (chr5-16458550-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033414.3(ZNF622):c.1129G>A(p.Asp377Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

ZNF622
NM_033414.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.66

Variant links:

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]

ZNF622 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1680454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF622	NM_033414.3 link	c.1129G>A	p.Asp377Asn	missense_variant	Exon 4 of 6	ENST00000308683.3	NP_219482.1	Q969S3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF622	ENST00000308683.3 link	c.1129G>A	p.Asp377Asn	missense_variant	Exon 4 of 6	1	NM_033414.3	ENSP00000310042.2		Q969S3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1129G>A (p.D377N) alteration is located in exon 4 (coding exon 4) of the ZNF622 gene. This alteration results from a G to A substitution at nucleotide position 1129, causing the aspartic acid (D) at amino acid position 377 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

Eigen

Benign

-0.065

Eigen_PC

Benign

-0.021

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Benign

0.017

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.22

Sift

Benign

0.085

Sift4G

Benign

0.10

Polyphen

0.45

Vest4

0.31

MutPred

0.29

Loss of loop (P = 0.0603);

MVP

0.26

MPC

0.41

ClinPred

0.75

GERP RS

4.8

Varity_R

0.23

gMVP

0.60

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over