5-150896165-G-T

Variant names:

• chr5-150896165-G-T
• NM_052860.4:c.1074C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052860.4(ZNF300):​c.1074C>A​(p.Cys358*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF300 NM_052860.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF300	NM_052860.4	c.1074C>A	p.Cys358*	stop_gained	Exon 6 of 6	ENST00000274599.10	NP_443092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF300	ENST00000274599.10	c.1074C>A	p.Cys358*	stop_gained	Exon 6 of 6	1	NM_052860.4	ENSP00000274599.5
ZNF300	ENST00000446148.7	c.1074C>A	p.Cys358*	stop_gained	Exon 7 of 7	1		ENSP00000397178.3
IRGM	ENST00000520549.1	n.*141-4424G>T		intron_variant	Intron 3 of 3	1		ENSP00000429819.1
ZNF300	ENST00000427179	c.*1889C>A		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000414195.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	30
DANN	Uncertain	0.99
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.0045	N
Vest4		0.23
GERP RS		2.5

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.

Other links and lift over

hg19: chr5-150275727;