rs2290989

Positions:

• chr5-150903222-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052860.4(ZNF300):​c.-27-40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 1,613,650 control chromosomes in the GnomAD database, including 2,053 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 0.039 (177 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1876 hom.)
• Consequence: ZNF300 NM_052860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF300	NM_052860.4	c.-27-40A>G		intron_variant		ENST00000274599.10
ZNF300	XM_047417874.1	c.-210A>G		5_prime_UTR_variant	1/5
ZNF300	NM_001172831.3	c.22-40A>G		intron_variant
ZNF300	NM_001172832.3	c.-94+642A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF300	ENST00000274599.10	c.-27-40A>G		intron_variant		1	NM_052860.4	P1
ZNF300	ENST00000446148.7	c.-27-40A>G		intron_variant		1		P1
ZNF300	ENST00000427179.5	c.-27-40A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5894 AN: 152120 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0368

GnomAD3 exomes AF: 0.0479 AC: 12011 AN: 250956 Hom.: 457 AF XY: 0.0496 AC XY: 6726 AN XY: 135662

Gnomad AFR exome AF: 0.0150

Gnomad AMR exome AF: 0.0174

Gnomad ASJ exome AF: 0.0380

Gnomad EAS exome AF: 0.166

Gnomad SAS exome AF: 0.0629

Gnomad FIN exome AF: 0.0313

Gnomad NFE exome AF: 0.0430

Gnomad OTH exome AF: 0.0437

GnomAD4 exome AF: 0.0447 AC: 65313 AN: 1461412 Hom.: 1876 Cov.: 33 AF XY: 0.0454 AC XY: 32985 AN XY: 727032

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.0399

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.0623

Gnomad4 FIN exome AF: 0.0297

Gnomad4 NFE exome AF: 0.0420

Gnomad4 OTH exome AF: 0.0459

GnomAD4 genome AF: 0.0387 AC: 5890 AN: 152238 Hom.: 177 Cov.: 32 AF XY: 0.0400 AC XY: 2980 AN XY: 74442

Gnomad4 AFR AF: 0.0166

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.0636

Gnomad4 FIN AF: 0.0326

Gnomad4 NFE AF: 0.0427

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0428 Hom.: 92

Bravo AF: 0.0395

Asia WGS AF: 0.0800 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.39
DANN	Benign	0.50

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: rs2290989; hg19: chr5-150282784; COSMIC: COSV51057244; COSMIC: COSV51057244;