5-150896590-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_052860.4(ZNF300):c.649G>A(p.Gly217Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,613,680 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (112 hom.)
• Consequence: ZNF300 NM_052860.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.149

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025434494).
• BP6: Variant 5-150896590-C-T is Benign according to our data. Variant chr5-150896590-C-T is described in ClinVar as [Benign]. Clinvar id is 771385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF300	NM_052860.4	c.649G>A	p.Gly217Arg	missense_variant	6/6	ENST00000274599.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF300	ENST00000274599.10	c.649G>A	p.Gly217Arg	missense_variant	6/6	1	NM_052860.4	P1
ZNF300	ENST00000446148.7	c.649G>A	p.Gly217Arg	missense_variant	7/7	1		P1
IRGM	ENST00000520549.1	c.*141-3999C>T		intron_variant, NMD_transcript_variant		1
ZNF300	ENST00000427179.5	c.*1464G>A		3_prime_UTR_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.00341 AC: 519 AN: 152098 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00897 AC: 2247 AN: 250522 Hom.: 89 AF XY: 0.00666 AC XY: 902 AN XY: 135524

Gnomad AFR exome AF: 0.000625

Gnomad AMR exome AF: 0.0629

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00136

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00688

GnomAD4 exome AF: 0.00206 AC: 3013 AN: 1461464 Hom.: 112 Cov.: 32 AF XY: 0.00176 AC XY: 1279 AN XY: 727028

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.0577

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00804

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00348 AC: 530 AN: 152216 Hom.: 9 Cov.: 32 AF XY: 0.00388 AC XY: 289 AN XY: 74436

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.000421 Hom.: 2

Bravo AF: 0.00599

ExAC AF: 0.00685 AC: 831

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 09, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	15
Dann	Benign	0.97
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.00025	N
LIST_S2	Benign	0.084	T;T;T;T
MetaRNN	Benign	0.0025	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.83	D;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.047
Sift	Benign	0.057	T;D;D;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.18	.;B;.;.
Vest4		0.27
MutPred		0.30		.;Gain of MoRF binding (P = 0.0068);.;Gain of MoRF binding (P = 0.0068);
MVP		0.21
MPC		0.19
ClinPred		0.015	T
GERP RS		3.0
Varity_R		0.11
gMVP		0.043

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: rs148132991; hg19: chr5-150276152;