3-121570652-C-T

Variant names:

• chr3-121570652-C-T
• rs12485719
• NM_001012659.2:c.-12-50C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012659.2. 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
	ARGFX	NM_001012659.2	MANE Select	c.-12-50C>T		intron	N/A	NP_001012677.1	A6NJG6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARGFX	ENST00000334384.5	TSL:3 MANE Select	c.-12-50C>T		intron	N/A	ENSP00000335578.3	A6NJG6
	ARGFX	ENST00000651603.1		c.-62C>T		upstream_gene	N/A	ENSP00000498601.1	A6NJG6

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

African (AFR) AF: 0.143 AC: 3537 AN: 24742

American (AMR) AF: 0.524 AC: 17263 AN: 32960

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 5080 AN: 20796

East Asian (EAS) AF: 0.0702 AC: 2412 AN: 34380

South Asian (SAS) AF: 0.119 AC: 7705 AN: 64978

European-Finnish (FIN) AF: 0.238 AC: 12197 AN: 51188

Middle Eastern (MID) AF: 0.172 AC: 699 AN: 4064

European-Non Finnish (NFE) AF: 0.272 AC: 224505 AN: 825972

Other (OTH) AF: 0.237 AC: 11323 AN: 47746

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

African (AFR) AF: 0.142 AC: 5906 AN: 41512

American (AMR) AF: 0.405 AC: 6183 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3470

East Asian (EAS) AF: 0.0654 AC: 339 AN: 5182

South Asian (SAS) AF: 0.115 AC: 556 AN: 4822

European-Finnish (FIN) AF: 0.235 AC: 2483 AN: 10566

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18608 AN: 67984

Other (OTH) AF: 0.231 AC: 487 AN: 2110

Alfa AF: 0.262 Hom.: 23483

Bravo AF: 0.249

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.30
DANN	Benign	0.81
PhyloP100		-1.9
PromoterAI		-0.029	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

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