Variant 1-90020819-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The ENST00000340281.9(ZNF326):c.1202A>G(p.Lys401Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,074 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF326
ENST00000340281.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

Variant links:

Genes affected

ZNF326 (HGNC:14104): (zinc finger protein 326) Enables RNA polymerase II complex binding activity. Involved in regulation of DNA-templated transcription, elongation and regulation of RNA splicing. Located in nucleoplasm. Part of DBIRD complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNF326 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity ZN326_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF326	NM_182976.4 linkuse as main transcript	c.1202A>G	p.Lys401Arg	missense_variant	10/12	ENST00000340281.9	NP_892021.1	Q5BKZ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF326	ENST00000340281.9 linkuse as main transcript	c.1202A>G	p.Lys401Arg	missense_variant	10/12	1	NM_182976.4	ENSP00000340796.4	Q5BKZ1-1
ZNF326	ENST00000370447.3 linkuse as main transcript	c.935A>G	p.Lys312Arg	missense_variant	10/12	1		ENSP00000359476.2	A0A0A0MRN4
ZNF326	ENST00000394583.7 linkuse as main transcript	n.*576A>G		non_coding_transcript_exon_variant	8/10	1		ENSP00000378084.3	E2QRN4
ZNF326	ENST00000394583.7 linkuse as main transcript	n.*576A>G		3_prime_UTR_variant	8/10	1		ENSP00000378084.3	E2QRN4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248680

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134476

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000165

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725262

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

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

Jun 07, 2023

The c.1202A>G (p.K401R) alteration is located in exon 10 (coding exon 10) of the ZNF326 gene. This alteration results from a A to G substitution at nucleotide position 1202, causing the lysine (K) at amino acid position 401 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.081

T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

T;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.27

Sift

Benign

0.16

T;T

Sift4G

Uncertain

0.013

D;D

Polyphen

0.96

D;.

Vest4

0.32

MutPred

0.78

Loss of ubiquitination at K401 (P = 0.0224);.;

MVP

0.37

MPC

0.24

ClinPred

0.36

GERP RS

5.6

Varity_R

0.17

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.24

Position offset: -27

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