19-12273103-C-T

Variant summary

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

The NM_016264.4(ZNF44):​c.1152G>A​(p.Met384Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M384V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF44
NM_016264.4 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.725
Variant links:
Genes affected
ZNF44 (HGNC:13110): (zinc finger protein 44) 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 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=0.07433453).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF44NM_016264.4 linkc.1152G>A p.Met384Ile missense_variant Exon 4 of 4 ENST00000355684.6 NP_057348.3 F8W7T7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF44ENST00000355684.6 linkc.1152G>A p.Met384Ile missense_variant Exon 4 of 4 2 NM_016264.4 ENSP00000347910.5 F8W7T7

Frequencies

GnomAD3 genomes
AF:
0.0000921
AC:
14
AN:
152010
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
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:
0.000479
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251264
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.000309
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
AF:
0.00000479
AC:
7
AN:
1461724
Hom.:
0
Cov.:
34
AF XY:
0.00000413
AC XY:
3
AN XY:
727134
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
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:
0.0000497
GnomAD4 genome
AF:
0.0000921
AC:
14
AN:
152010
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.000314
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:
0.000479
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000945
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 01, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1296G>A (p.M432I) alteration is located in exon 5 (coding exon 5) of the ZNF44 gene. This alteration results from a G to A substitution at nucleotide position 1296, causing the methionine (M) at amino acid position 432 to be replaced by an isoleucine (I). 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
Uncertain
0.44
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0063
T;.
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.000010
N
LIST_S2
Benign
0.16
T;T
M_CAP
Benign
0.0010
T
MetaRNN
Benign
0.074
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;.
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.067
Sift
Benign
0.046
D;D
Sift4G
Uncertain
0.014
D;D
Polyphen
0.98
D;D
Vest4
0.18
MutPred
0.36
Loss of disorder (P = 0.0779);.;
MVP
0.29
MPC
0.38
ClinPred
0.33
T
GERP RS
-1.8
Varity_R
0.17
gMVP
0.029

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: rs373408667; hg19: chr19-12383918; API