dbSNP rs147702441: ZNF300:p.Arg541Leu (chr5-150895617-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_052860.4(ZNF300):c.1622G>T(p.Arg541Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF300
NM_052860.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0930

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]

ZNF300 links:

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]

IRGM links:

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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=0.25006524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF300	NM_052860.4 link	c.1622G>T	p.Arg541Leu	missense_variant	Exon 6 of 6	ENST00000274599.10	NP_443092.1	Q96RE9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF300	ENST00000274599.10 link	c.1622G>T	p.Arg541Leu	missense_variant	Exon 6 of 6	1	NM_052860.4	ENSP00000274599.5	Q96RE9-1
ZNF300	ENST00000446148.7 link	c.1622G>T	p.Arg541Leu	missense_variant	Exon 7 of 7	1		ENSP00000397178.3	Q96RE9-3
IRGM	ENST00000520549.1 link	n.*141-4972C>A		intron_variant	Intron 3 of 3	1		ENSP00000429819.1	A0A9H4B933
ZNF300	ENST00000427179 link	c.*2437G>T		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000414195.1	F8WE31

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726792

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;T;.;.

Eigen

Benign

-0.038

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.00068

LIST_S2

Benign

0.63

T;T;T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L;.;.

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-6.1

D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

0.97

.;D;.;.

Vest4

0.35

MutPred

0.61

.;Loss of phosphorylation at T544 (P = 0.0506);.;Loss of phosphorylation at T544 (P = 0.0506);

MVP

0.41

MPC

0.53

ClinPred

0.92

GERP RS

2.7

Varity_R

0.39

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over