Genetic Variant ZNF300:p.Ser338Ser (chr5-150896225-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.57

Publications

11 publications found

Variant links:

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]

ZNF300 links:

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]

IRGM links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF300	NM_052860.4 link	c.1014G>A	p.Ser338Ser	synonymous_variant	Exon 6 of 6	ENST00000274599.10	NP_443092.1	Q96RE9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF300	ENST00000274599.10 link	c.1014G>A	p.Ser338Ser	synonymous_variant	Exon 6 of 6	1	NM_052860.4	ENSP00000274599.5	Q96RE9-1
ZNF300	ENST00000446148.7 link	c.1014G>A	p.Ser338Ser	synonymous_variant	Exon 7 of 7	1		ENSP00000397178.3	Q96RE9-3
IRGM	ENST00000520549.1 link	n.*141-4364C>T		intron_variant	Intron 3 of 3	1		ENSP00000429819.1	A0A9H4B933
ZNF300	ENST00000427179.5 link	c.*1829G>A		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000414195.1	F8WE31

Frequencies

GnomAD3 genomes

AF:

0.0443

AC:

6730

AN:

151830

Hom.:

200

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0458

AC XY:

33330

AN XY:

726968

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

3768

7537

11305

15074

18842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1810

3620

5430

7240

9050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0443

AC:

6728

AN:

151948

Hom.:

199

Cov.:

AF XY:

0.0451

AC XY:

3352

AN XY:

74280

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.0428

AC:

2907

AN:

67946

Other (OTH)

AF:

0.0379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

335

671

1006

1342

1677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0427

Hom.:

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

(source)

DANN

Benign

0.83

PhyloP100

-3.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over