Variant chr3-121586239-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001012659.2(ARGFX):c.587C>T(p.Thr196Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.005 in 1,614,032 control chromosomes in the GnomAD database, including 359 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.027 ( 182 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 177 hom. )

Consequence

ARGFX
NM_001012659.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.159

Variant links:

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]

ARGFX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025942028).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARGFX	NM_001012659.2 linkuse as main transcript	c.587C>T	p.Thr196Ile	missense_variant	5/5	ENST00000334384.5	NP_001012677.1	A6NJG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARGFX	ENST00000334384.5 linkuse as main transcript	c.587C>T	p.Thr196Ile	missense_variant	5/5	3	NM_001012659.2	ENSP00000335578.3		A6NJG6
ARGFX	ENST00000651603.1 linkuse as main transcript	c.587C>T	p.Thr196Ile	missense_variant	4/4			ENSP00000498601.1		A6NJG6

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

4051

AN:

152152

Hom.:

182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0922

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00701

AC:

1760

AN:

251170

Hom.:

AF XY:

0.00530

AC XY:

720

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.0966

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00274

AC:

4006

AN:

1461762

Hom.:

177

Cov.:

AF XY:

0.00239

AC XY:

1738

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0939

Gnomad4 AMR exome

AF:

0.00472

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000170

Gnomad4 OTH exome

AF:

0.00667

GnomAD4 genome

AF:

0.0267

AC:

4060

AN:

152270

Hom.:

182

Cov.:

AF XY:

0.0255

AC XY:

1899

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0921

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0140

Hom.:

Bravo

AF:

0.0297

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0897

AC:

395

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00867

AC:

1053

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.017

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.70

REVEL

Benign

0.22

Sift

Benign

0.65

Sift4G

Benign

0.069

Polyphen

0.97

Vest4

0.11

MVP

0.48

MPC

0.28

ClinPred

0.014

GERP RS

2.1

Varity_R

0.044

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over