19-12074127-C-G

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

19

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]

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
ZNF844NM_001136501.3 linkc.100C>G p.Gln34Glu missense_variant Exon 2 of 4 ENST00000439326.8 NP_001129973.1 Q08AG5B4DSG8
ZNF844NR_134326.2 linkn.243C>G non_coding_transcript_exon_variant Exon 2 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF844ENST00000439326.8 linkc.100C>G p.Gln34Glu missense_variant Exon 2 of 4 1 NM_001136501.3 ENSP00000392024.3 Q08AG5
ENSG00000286098ENST00000652448.1 linkc.4C>G p.Gln2Glu missense_variant Exon 3 of 5 ENSP00000498410.1 A0A494C069
ZNF844ENST00000441304.2 linkc.100C>G p.Gln34Glu missense_variant Exon 2 of 3 1 ENSP00000402097.2 F8WE48
ZNF844ENST00000550826.1 linkc.-280-1185C>G intron_variant Intron 1 of 1 3 ENSP00000448588.1 F8VS19

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152136
Hom.:
0
Cov.:
32
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:
2
AN:
251102
Hom.:
0
AF XY:
0.00000736
AC XY:
1
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.:
31
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152136
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
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:
1

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
T
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
N
LIST_S2
Benign
0.14
T;T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.047
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.0
L;.
PrimateAI
Benign
0.26
T
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
T
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.

Other links and lift over

dbSNP: rs770133937; hg19: chr19-12184942; API