Variant 5-16451772-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033414.3(ZNF622):c.1319T>A(p.Met440Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,613,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

ZNF622
NM_033414.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.147

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004706621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF622	NM_033414.3 linkuse as main transcript	c.1319T>A	p.Met440Lys	missense_variant	6/6	ENST00000308683.3	NP_219482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF622	ENST00000308683.3 linkuse as main transcript	c.1319T>A	p.Met440Lys	missense_variant	6/6	1	NM_033414.3	ENSP00000310042	P1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000355

AC:

AN:

250580

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

135440

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000361

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.000655

GnomAD4 exome

AF:

0.000249

AC:

364

AN:

1461302

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

179

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000557

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000187

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000276

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000380

Hom.:

Bravo

AF:

0.000257

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000362

AC:

EpiCase

AF:

0.000818

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.1319T>A (p.M440K) alteration is located in exon 6 (coding exon 6) of the ZNF622 gene. This alteration results from a T to A substitution at nucleotide position 1319, causing the methionine (M) at amino acid position 440 to be replaced by a lysine (K). 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

0.089

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.9

DANN

Benign

0.56

DEOGEN2

Benign

0.0083

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.66

M_CAP

Benign

0.0035

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.070

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

1.2

REVEL

Benign

0.095

Sift

Benign

0.97

Sift4G

Benign

0.95

Polyphen

0.026

Vest4

0.19

MVP

0.13

MPC

0.51

ClinPred

0.016

GERP RS

-0.16

Varity_R

0.073

gMVP

0.47

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