rs17800771

Variant names:

• chr5-150896225-C-T
• rs17800771
• NM_052860.4:c.1014G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_052860.4(ZNF300):​c.1014G>A​(p.Ser338Ser) 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
• Publications: 11 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: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF300	NM_052860.4	MANE Select	c.1014G>A	p.Ser338Ser	synonymous	Exon 6 of 6	NP_443092.1	Q96RE9-1
	ZNF300	NM_001172831.3		c.1062G>A	p.Ser354Ser	synonymous	Exon 7 of 7	NP_001166302.1	Q96RE9-3
	ZNF300	NM_001172832.3		c.906G>A	p.Ser302Ser	synonymous	Exon 5 of 5	NP_001166303.1	Q96RE9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF300	ENST00000274599.10	TSL:1 MANE Select	c.1014G>A	p.Ser338Ser	synonymous	Exon 6 of 6	ENSP00000274599.5	Q96RE9-1
	ZNF300	ENST00000446148.7	TSL:1	c.1014G>A	p.Ser338Ser	synonymous	Exon 7 of 7	ENSP00000397178.3	Q96RE9-1
	IRGM	ENST00000520549.1	TSL:1	n.*141-4364C>T		intron	N/A	ENSP00000429819.1	A0A9H4B933

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

GnomAD2 exomes AF: 0.0493 AC: 12317 AN: 250066 AF XY: 0.0505

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 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

African (AFR) AF: 0.0394 AC: 1319 AN: 33458

American (AMR) AF: 0.0200 AC: 892 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 1038 AN: 26106

East Asian (EAS) AF: 0.150 AC: 5934 AN: 39680

South Asian (SAS) AF: 0.0618 AC: 5330 AN: 86224

European-Finnish (FIN) AF: 0.0293 AC: 1567 AN: 53396

Middle Eastern (MID) AF: 0.0706 AC: 407 AN: 5764

European-Non Finnish (NFE) AF: 0.0421 AC: 46809 AN: 1111762

Other (OTH) AF: 0.0471 AC: 2844 AN: 60374

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

African (AFR) AF: 0.0361 AC: 1495 AN: 41438

American (AMR) AF: 0.0328 AC: 500 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3466

East Asian (EAS) AF: 0.161 AC: 825 AN: 5126

South Asian (SAS) AF: 0.0628 AC: 302 AN: 4812

European-Finnish (FIN) AF: 0.0328 AC: 347 AN: 10592

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.0428 AC: 2907 AN: 67946

Other (OTH) AF: 0.0379 AC: 80 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

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