rs3746554

Positions:

• chr20-49270339-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021035.3(ZNFX1):​c.1473A>G​(p.Gln491Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,614,170 control chromosomes in the GnomAD database, including 722 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 0.015 (61 hom., cov: 32)
  • Exomes 𝑓: 0.021 (661 hom.)
• Consequence: ZNFX1 NM_021035.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

Genes affected

ZNFX1 (HGNC:29271): (zinc finger NFX1-type containing 1) Enables RNA binding activity. Predicted to be involved in heterochromatin assembly by small RNA. Predicted to be part of nuclear RNA-directed RNA polymerase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=0.011 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNFX1	NM_021035.3	c.1473A>G	p.Gln491Gln	synonymous_variant	3/14	ENST00000396105.6	NP_066363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNFX1	ENST00000396105.6	c.1473A>G	p.Gln491Gln	synonymous_variant	3/14	1	NM_021035.3	ENSP00000379412.1

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2323 AN: 152236 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.0611

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.00838

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.0249 AC: 6229 AN: 250624 Hom.: 173 AF XY: 0.0257 AC XY: 3482 AN XY: 135484

Gnomad AFR exome AF: 0.00327

Gnomad AMR exome AF: 0.0354

Gnomad ASJ exome AF: 0.00627

Gnomad EAS exome AF: 0.0496

Gnomad SAS exome AF: 0.0656

Gnomad FIN exome AF: 0.00971

Gnomad NFE exome AF: 0.0144

Gnomad OTH exome AF: 0.0213

GnomAD4 exome AF: 0.0207 AC: 30262 AN: 1461816 Hom.: 661 Cov.: 35 AF XY: 0.0217 AC XY: 15778 AN XY: 727204

Gnomad4 AFR exome AF: 0.00293

Gnomad4 AMR exome AF: 0.0345

Gnomad4 ASJ exome AF: 0.00639

Gnomad4 EAS exome AF: 0.0913

Gnomad4 SAS exome AF: 0.0632

Gnomad4 FIN exome AF: 0.0100

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0213

GnomAD4 genome AF: 0.0153 AC: 2329 AN: 152354 Hom.: 61 Cov.: 32 AF XY: 0.0163 AC XY: 1212 AN XY: 74514

Gnomad4 AFR AF: 0.00284

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.0612

Gnomad4 SAS AF: 0.0710

Gnomad4 FIN AF: 0.00838

Gnomad4 NFE AF: 0.0149

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0151 Hom.: 36

Bravo AF: 0.0142

Asia WGS AF: 0.0890 AC: 309 AN: 3478

EpiCase AF: 0.0138

EpiControl AF: 0.0139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.6
DANN	Benign	0.66

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: rs3746554; hg19: chr20-47886876; COSMIC: COSV65579104;