Variant chr5-150010222-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014983.3(HMGXB3):c.424C>T(p.Arg142Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,551,850 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R142Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

HMGXB3
NM_014983.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

HMGXB3 (HGNC:28982): (HMG-box containing 3) This gene is one of the non-canonical high mobility group (HMG) genes. The encoded protein contains an HMG-box domain found in DNA binding proteins such as transcription factors and chromosomal proteins. [provided by RefSeq, Aug 2011]

HMGXB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0041986406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HMGXB3	NM_014983.3 linkuse as main transcript	c.424C>T	p.Arg142Trp	missense_variant	4/20	ENST00000502717.6
HMGXB3	XM_047416963.1 linkuse as main transcript	c.424C>T	p.Arg142Trp	missense_variant	4/12
HMGXB3	NM_001366501.2 linkuse as main transcript	c.313-2033C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HMGXB3	ENST00000502717.6 linkuse as main transcript	c.424C>T	p.Arg142Trp	missense_variant	4/20	1	NM_014983.3	P2
HMGXB3	ENST00000613459.4 linkuse as main transcript	c.1162C>T	p.Arg388Trp	missense_variant	5/21	5		A2
HMGXB3	ENST00000503427.5 linkuse as main transcript	c.424C>T	p.Arg142Trp	missense_variant	4/21	5		A2

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000178

AC:

AN:

157280

Hom.:

AF XY:

0.000168

AC XY:

AN XY:

83200

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000161

AC:

226

AN:

1399620

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

111

AN XY:

690308

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000161

Gnomad4 OTH exome

AF:

0.000155

GnomAD4 genome

AF:

0.000512

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000388

Hom.:

Bravo

AF:

0.000544

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000216

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.424C>T (p.R142W) alteration is located in exon 4 (coding exon 3) of the HMGXB3 gene. This alteration results from a C to T substitution at nucleotide position 424, causing the arginine (R) at amino acid position 142 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.092

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0042

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.

MutationTaster

Benign

0.73

N;N

PrimateAI

Benign

0.35

Sift4G

Benign

0.066

T;T;T

Polyphen

0.014

B;.;.

Vest4

0.32

MVP

0.19

ClinPred

0.018

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.078

gMVP

0.65

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over