3-121570652-C-T

Position:

• chr3-121570652-C-T

Variant summary

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

The NM_001012659.2(ARGFX):​c.-12-50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,258,930 control chromosomes in the GnomAD database, including 44,466 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 0.24 (4939 hom., cov: 32)
  • Exomes 𝑓: 0.26 (39527 hom.)
• Consequence: ARGFX NM_001012659.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

Genes affected

ARGFX (HGNC:30146): (arginine-fifty homeobox) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the ARGFX homeobox gene family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARGFX	NM_001012659.2	c.-12-50C>T		intron_variant		ENST00000334384.5	NP_001012677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARGFX	ENST00000334384.5	c.-12-50C>T		intron_variant		3	NM_001012659.2	ENSP00000335578.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35812 AN: 151986 Hom.: 4921 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0653

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.257 AC: 284721 AN: 1106826 Hom.: 39527 AF XY: 0.252 AC XY: 140494 AN XY: 557158

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.0702

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.236 AC: 35868 AN: 152104 Hom.: 4939 Cov.: 32 AF XY: 0.235 AC XY: 17463 AN XY: 74350

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0654

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.231

Alfa AF: 0.262 Hom.: 11531

Bravo AF: 0.249

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.30
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12485719; hg19: chr3-121289499; COSMIC: COSV57681931;