NM_052860.4:c.1788G>C

Variant names:

• chr5-150895451-C-G
• rs139710646
• NM_052860.4:c.1788G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_052860.4(ZNF300):​c.1788G>C​(p.Gln596His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,608,834 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: ZNF300 NM_052860.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.302
• Publications: 0 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1360982).

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.1788G>C	p.Gln596His	missense	Exon 6 of 6	NP_443092.1	Q96RE9-1
	ZNF300	NM_001172831.3		c.1836G>C	p.Gln612His	missense	Exon 7 of 7	NP_001166302.1	Q96RE9-3
	ZNF300	NM_001172832.3		c.1680G>C	p.Gln560His	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.1788G>C	p.Gln596His	missense	Exon 6 of 6	ENSP00000274599.5	Q96RE9-1
	ZNF300	ENST00000446148.7	TSL:1	c.1788G>C	p.Gln596His	missense	Exon 7 of 7	ENSP00000397178.3	Q96RE9-1
	IRGM	ENST00000520549.1	TSL:1	n.*141-5138C>G		intron	N/A	ENSP00000429819.1	A0A9H4B933

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000883

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000105 AC: 26 AN: 248782 AF XY: 0.0000893

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000585

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000196

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000187 AC: 273 AN: 1456740 Hom.: 1 Cov.: 31 AF XY: 0.000182 AC XY: 132 AN XY: 724000

African (AFR) AF: 0.0000900 AC: 3 AN: 33324

American (AMR) AF: 0.0000451 AC: 2 AN: 44350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.00 AC: 0 AN: 85740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.000234 AC: 260 AN: 1108826

Other (OTH) AF: 0.000133 AC: 8 AN: 60148

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.000131 AC: 2 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000566 Hom.: 0

Bravo AF: 0.000102

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000124 AC: 15

EpiCase AF: 0.000273

EpiControl AF: 0.000297

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	Uncertain	0.47
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.30
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.075
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.011	D
Polyphen		0.19	B
Vest4		0.19
MutPred		0.61		Loss of MoRF binding (P = 0.094)
MVP		0.50
MPC		0.61
ClinPred		0.10	T
GERP RS		3.1
Varity_R		0.50
gMVP		0.10
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

Other links and lift over

dbSNP: rs139710646; hg19: chr5-150275013;