rs201176485

Variant names:

• chr5-150895692-G-A
• rs201176485
• NM_052860.4:c.1547C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_052860.4(ZNF300):​c.1547C>T​(p.Thr516Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000215 in 1,613,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: ZNF300 NM_052860.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04
• Publications: 2 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29496157).

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.1547C>T	p.Thr516Ile	missense	Exon 6 of 6	NP_443092.1	Q96RE9-1
	ZNF300	NM_001172831.3		c.1595C>T	p.Thr532Ile	missense	Exon 7 of 7	NP_001166302.1	Q96RE9-3
	ZNF300	NM_001172832.3		c.1439C>T	p.Thr480Ile	missense	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.1547C>T	p.Thr516Ile	missense	Exon 6 of 6	ENSP00000274599.5	Q96RE9-1
	ZNF300	ENST00000446148.7	TSL:1	c.1547C>T	p.Thr516Ile	missense	Exon 7 of 7	ENSP00000397178.3	Q96RE9-1
	IRGM	ENST00000520549.1	TSL:1	n.*141-4897G>A		intron	N/A	ENSP00000429819.1	A0A9H4B933

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152112 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000678 AC: 17 AN: 250612 AF XY: 0.0000517

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000227 AC: 331 AN: 1461354 Hom.: 0 Cov.: 31 AF XY: 0.000227 AC XY: 165 AN XY: 726948

African (AFR) AF: 0.0000897 AC: 3 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000280 AC: 311 AN: 1111796

Other (OTH) AF: 0.000282 AC: 17 AN: 60370

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74332

African (AFR) AF: 0.0000241 AC: 1 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68012

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000163 Hom.: 0

Bravo AF: 0.000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.25
Sift	Benign	0.046	D
Sift4G	Benign	0.077	T
Polyphen		1.0	D
Vest4		0.49
MVP		0.34
MPC		0.66
ClinPred		0.59	D
GERP RS		3.9
Varity_R		0.36
gMVP		0.062
Mutation Taster		=93/7	polymorphism

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: rs201176485; hg19: chr5-150275254;