rs17800771

chr5-150896225-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_052860.4(ZNF300):c.1014G>A(p.Ser338=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 1,613,318 control chromosomes in the GnomAD database, including 2,102 homozygotes. 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: 𝑓 0.044 (199 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1903 hom.)
• Consequence: ZNF300 NM_052860.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-3.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF300	NM_052860.4	c.1014G>A	p.Ser338=	synonymous_variant	6/6	ENST00000274599.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF300	ENST00000274599.10	c.1014G>A	p.Ser338=	synonymous_variant	6/6	1	NM_052860.4	P1
ZNF300	ENST00000446148.7	c.1014G>A	p.Ser338=	synonymous_variant	7/7	1		P1
IRGM	ENST00000520549.1	c.*141-4364C>T		intron_variant, NMD_transcript_variant		1
ZNF300	ENST00000427179.5	c.*1829G>A		3_prime_UTR_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.0443 AC: 6730 AN: 151830 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.0388

GnomAD3 exomes AF: 0.0493 AC: 12317 AN: 250066 Hom.: 465 AF XY: 0.0505 AC XY: 6839 AN XY: 135466

Gnomad AFR exome AF: 0.0355

Gnomad AMR exome AF: 0.0184

Gnomad ASJ exome AF: 0.0380

Gnomad EAS exome AF: 0.166

Gnomad SAS exome AF: 0.0625

Gnomad FIN exome AF: 0.0309

Gnomad NFE exome AF: 0.0428

Gnomad OTH exome AF: 0.0434

GnomAD4 exome AF: 0.0453 AC: 66140 AN: 1461370 Hom.: 1903 Cov.: 32 AF XY: 0.0458 AC XY: 33330 AN XY: 726968

Gnomad4 AFR exome AF: 0.0394

Gnomad4 AMR exome AF: 0.0200

Gnomad4 ASJ exome AF: 0.0398

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.0618

Gnomad4 FIN exome AF: 0.0293

Gnomad4 NFE exome AF: 0.0421

Gnomad4 OTH exome AF: 0.0471

GnomAD4 genome AF: 0.0443 AC: 6728 AN: 151948 Hom.: 199 Cov.: 32 AF XY: 0.0451 AC XY: 3352 AN XY: 74280

Gnomad4 AFR AF: 0.0361

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.0628

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0428

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0427 Hom.: 56

Bravo AF: 0.0459

Asia WGS AF: 0.0810 AC: 280 AN: 3478

EpiCase AF: 0.0446

EpiControl AF: 0.0429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	13
Dann	Benign	0.83

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

Other links and lift over

dbSNP: rs17800771; hg19: chr5-150275787; COSMIC: COSV51057101;