5-150896165-G-A

Variant names:

• chr5-150896165-G-A
• rs148013564
• NM_052860.4:c.1074C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_052860.4(ZNF300):​c.1074C>T​(p.Cys358Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00075 in 1,612,918 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (7 hom.)
• Consequence: ZNF300 NM_052860.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.269

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 5-150896165-G-A is Benign according to our data. Variant chr5-150896165-G-A is described in ClinVar as [Benign]. Clinvar id is 776080.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.269 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF300	NM_052860.4	c.1074C>T	p.Cys358Cys	synonymous_variant	Exon 6 of 6	ENST00000274599.10	NP_443092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF300	ENST00000274599.10	c.1074C>T	p.Cys358Cys	synonymous_variant	Exon 6 of 6	1	NM_052860.4	ENSP00000274599.5
ZNF300	ENST00000446148.7	c.1074C>T	p.Cys358Cys	synonymous_variant	Exon 7 of 7	1		ENSP00000397178.3
IRGM	ENST00000520549.1	n.*141-4424G>A		intron_variant	Intron 3 of 3	1		ENSP00000429819.1
ZNF300	ENST00000427179	c.*1889C>T		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000414195.1

Frequencies

GnomAD3 genomes AF: 0.00361 AC: 548 AN: 151734 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

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: 0.000103

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.000985 AC: 246 AN: 249860 AF XY: 0.000718

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.0000708

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000453 AC: 662 AN: 1461064 Hom.: 7 Cov.: 32 AF XY: 0.000391 AC XY: 284 AN XY: 726824

Gnomad4 AFR exome AF: 0.0157 AC: 525 AN: 33448

Gnomad4 AMR exome AF: 0.000583 AC: 26 AN: 44564

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26060

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39688

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86194

Gnomad4 FIN exome AF: 0.0000187 AC: 1 AN: 53338

Gnomad4 NFE exome AF: 0.0000558 AC: 62 AN: 1111668

Gnomad4 Remaining exome AF: 0.000729 AC: 44 AN: 60346

GnomAD4 genome AF: 0.00361 AC: 548 AN: 151854 Hom.: 4 Cov.: 32 AF XY: 0.00330 AC XY: 245 AN XY: 74220

Gnomad4 AFR AF: 0.0125 AC: 0.0125115 AN: 0.0125115

Gnomad4 AMR AF: 0.00111 AC: 0.00111417 AN: 0.00111417

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000208 AC: 0.00020816 AN: 0.00020816

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000103 AC: 0.000103075 AN: 0.000103075

Gnomad4 OTH AF: 0.00237 AC: 0.00237192 AN: 0.00237192

Alfa AF: 0.00166 Hom.: 1

Bravo AF: 0.00410

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 19, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.2
DANN	Benign	0.87
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs148013564; hg19: chr5-150275727;