chr5-150898347-A-C

Variant names:

• chr5-150898347-A-C
• rs11741861
• NM_052860.4:c.142+81T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052860.4(ZNF300):​c.142+81T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ZNF300 NM_052860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052860.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF300	NM_052860.4	MANE Select	c.142+81T>G		intron	N/A	NP_443092.1
	ZNF300	NM_001172831.3		c.190+81T>G		intron	N/A	NP_001166302.1
	ZNF300	NM_001172832.3		c.34+81T>G		intron	N/A	NP_001166303.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF300	ENST00000274599.10	TSL:1 MANE Select	c.142+81T>G		intron	N/A	ENSP00000274599.5
	ZNF300	ENST00000446148.7	TSL:1	c.142+81T>G		intron	N/A	ENSP00000397178.3
	IRGM	ENST00000520549.1	TSL:1	n.*141-2242A>C		intron	N/A	ENSP00000429819.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.9
DANN	Benign	0.43
PhyloP100		0.065

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

Other links and lift over

dbSNP: rs11741861; hg19: chr5-150277909;