Genetic Variant ZNF844:p.Gln34Glu (chr19-12074127-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001136501.3(ZNF844):c.100C>G(p.Gln34Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Consequence

ZNF844
NM_001136501.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.547

Variant links:

Genes affected

ZNF844 (HGNC:25932): (zinc finger protein 844) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF844 links:

ENSG00000286098 (HGNC:):

ENSG00000286098 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=0.046763897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF844	NM_001136501.3 link	c.100C>G	p.Gln34Glu	missense_variant	Exon 2 of 4	ENST00000439326.8	NP_001129973.1	Q08AG5B4DSG8
ZNF844	NR_134326.2 link	n.243C>G		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF844	ENST00000439326.8 link	c.100C>G	p.Gln34Glu	missense_variant	Exon 2 of 4	1	NM_001136501.3	ENSP00000392024.3	Q08AG5
ENSG00000286098	ENST00000652448.1 link	c.4C>G	p.Gln2Glu	missense_variant	Exon 3 of 5			ENSP00000498410.1	A0A494C069
ZNF844	ENST00000441304.2 link	c.100C>G	p.Gln34Glu	missense_variant	Exon 2 of 3	1		ENSP00000402097.2	F8WE48
ZNF844	ENST00000550826.1 link	c.-280-1185C>G		intron_variant	Intron 1 of 1	3		ENSP00000448588.1	F8VS19

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251102

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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

Cov.:

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

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

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.100C>G (p.Q34E) alteration is located in exon 2 (coding exon 2) of the ZNF844 gene. This alteration results from a C to G substitution at nucleotide position 100, causing the glutamine (Q) at amino acid position 34 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.3

DANN

Benign

0.85

DEOGEN2

Benign

0.0033

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.14

T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.059

Sift

Benign

0.21

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.013

B;.

Vest4

0.20

MVP

0.014

MPC

0.027

ClinPred

0.024

GERP RS

-3.0

Varity_R

0.042

gMVP

0.066

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