5-150010597-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014983.3(HMGXB3):c.799A>G(p.Thr267Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: HMGXB3 NM_014983.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06996724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGXB3	NM_014983.3	c.799A>G	p.Thr267Ala	missense_variant	4/20	ENST00000502717.6
HMGXB3	XM_047416963.1	c.799A>G	p.Thr267Ala	missense_variant	4/12
HMGXB3	NM_001366501.2	c.313-1658A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGXB3	ENST00000502717.6	c.799A>G	p.Thr267Ala	missense_variant	4/20	1	NM_014983.3	P2
HMGXB3	ENST00000613459.4	c.1537A>G	p.Thr513Ala	missense_variant	5/21	5		A2
HMGXB3	ENST00000503427.5	c.799A>G	p.Thr267Ala	missense_variant	4/21	5		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398270 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 689612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.799A>G (p.T267A) alteration is located in exon 4 (coding exon 3) of the HMGXB3 gene. This alteration results from a A to G substitution at nucleotide position 799, causing the threonine (T) at amino acid position 267 to be replaced by an alanine (A). 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	0.099
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0093	T;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.080
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N;.;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.54	T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.029	B;.;.
Vest4		0.082
MutPred		0.19		Loss of glycosylation at T513 (P = 0.0556);.;.;
MVP		0.15
ClinPred		0.24	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.093
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-149390160;