rs2290989

Variant names:

• chr5-150903222-T-C
• rs2290989
• NM_052860.4:c.-27-40A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF300	NM_052860.4	c.-27-40A>G		intron_variant	Intron 2 of 5	ENST00000274599.10	NP_443092.1
ZNF300	XM_047417874.1	c.-210A>G		5_prime_UTR_variant	Exon 1 of 5		XP_047273830.1
ZNF300	NM_001172831.3	c.22-40A>G		intron_variant	Intron 3 of 6		NP_001166302.1
ZNF300	NM_001172832.3	c.-94+642A>G		intron_variant	Intron 2 of 4		NP_001166303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF300	ENST00000274599.10	c.-27-40A>G		intron_variant	Intron 2 of 5	1	NM_052860.4	ENSP00000274599.5
ZNF300	ENST00000446148.7	c.-27-40A>G		intron_variant	Intron 3 of 6	1		ENSP00000397178.3
ZNF300	ENST00000427179.5	c.-27-40A>G		intron_variant	Intron 2 of 4	2		ENSP00000414195.1

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

GnomAD2 exomes AF: 0.0479 AC: 12011 AN: 250956 AF XY: 0.0496

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 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

African (AFR) AF: 0.0189 AC: 634 AN: 33472

American (AMR) AF: 0.0190 AC: 849 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0399 AC: 1042 AN: 26130

East Asian (EAS) AF: 0.150 AC: 5935 AN: 39672

South Asian (SAS) AF: 0.0623 AC: 5370 AN: 86238

European-Finnish (FIN) AF: 0.0297 AC: 1588 AN: 53402

Middle Eastern (MID) AF: 0.0697 AC: 402 AN: 5768

European-Non Finnish (NFE) AF: 0.0420 AC: 46719 AN: 1111642

Other (OTH) AF: 0.0459 AC: 2774 AN: 60372

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

African (AFR) AF: 0.0166 AC: 691 AN: 41534

American (AMR) AF: 0.0305 AC: 467 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3472

East Asian (EAS) AF: 0.160 AC: 827 AN: 5168

South Asian (SAS) AF: 0.0636 AC: 307 AN: 4826

European-Finnish (FIN) AF: 0.0326 AC: 345 AN: 10598

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0427 AC: 2905 AN: 68018

Other (OTH) AF: 0.0360 AC: 76 AN: 2112

Alfa AF: 0.0427 Hom.: 100

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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