chr5-150896410-C-T

Variant summary

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

The NM_052860.4(ZNF300):​c.829G>A​(p.Ala277Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 6.8e-7 ( 0 hom. )

Consequence

ZNF300
NM_052860.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.751
Variant links:
Genes affected
ZNF300 (HGNC:13091): (zinc finger protein 300) The protein encoded by this gene is a C2H2-type zinc finger DNA binding protein and likely transcriptional regulator. The function of this protein is not yet known. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]
IRGM (HGNC:29597): (immunity related GTPase M) This gene encodes a member of the p47 immunity-related GTPase family. The encoded protein may play a role in the innate immune response by regulating autophagy formation in response to intracellular pathogens. Polymorphisms that affect the normal expression of this gene are associated with a susceptibility to Crohn's disease and tuberculosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2016]

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=0.06358194).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF300NM_052860.4 linkuse as main transcriptc.829G>A p.Ala277Thr missense_variant 6/6 ENST00000274599.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF300ENST00000274599.10 linkuse as main transcriptc.829G>A p.Ala277Thr missense_variant 6/61 NM_052860.4 P1Q96RE9-1
ZNF300ENST00000446148.7 linkuse as main transcriptc.829G>A p.Ala277Thr missense_variant 7/71 P1Q96RE9-3
IRGMENST00000520549.1 linkuse as main transcriptc.*141-4179C>T intron_variant, NMD_transcript_variant 1
ZNF300ENST00000427179.5 linkuse as main transcriptc.*1644G>A 3_prime_UTR_variant 5/52

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00000399
AC:
1
AN:
250762
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135534
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
6.84e-7
AC:
1
AN:
1461400
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727002
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
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:
0.00000378

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 submitterclinical testingAmbry GeneticsMar 24, 2023The c.877G>A (p.A293T) alteration is located in exon 7 (coding exon 5) of the ZNF300 gene. This alteration results from a G to A substitution at nucleotide position 877, causing the alanine (A) at amino acid position 293 to be replaced by a threonine (T). 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
-0.38
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
17
DANN
Benign
0.69
DEOGEN2
Benign
0.17
.;T;.;.
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.00010
N
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.064
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
.;L;.;.
MutationTaster
Benign
0.92
D;N;N;N;N
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.4
N;D;D;D
REVEL
Benign
0.017
Sift
Benign
0.41
T;T;T;T
Sift4G
Benign
0.15
T;T;T;T
Polyphen
0.40
.;B;.;.
Vest4
0.081
MutPred
0.47
.;Loss of catalytic residue at A277 (P = 0.0528);.;Loss of catalytic residue at A277 (P = 0.0528);
MVP
0.25
MPC
0.40
ClinPred
0.19
T
GERP RS
0.58
Varity_R
0.085
gMVP
0.015

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: rs1385237648; hg19: chr5-150275972; API