5-150012297-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.853A>G(p.Ile285Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000357 in 1,400,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: HMGXB3 NM_014983.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.37

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=0.20097905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGXB3	NM_014983.3	c.853A>G	p.Ile285Val	missense_variant	5/20	ENST00000502717.6
HMGXB3	NM_001366501.2	c.355A>G	p.Ile119Val	missense_variant	4/19
HMGXB3	XM_047416963.1	c.853A>G	p.Ile285Val	missense_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGXB3	ENST00000502717.6	c.853A>G	p.Ile285Val	missense_variant	5/20	1	NM_014983.3	P2
HMGXB3	ENST00000613459.4	c.1591A>G	p.Ile531Val	missense_variant	6/21	5		A2
HMGXB3	ENST00000503427.5	c.853A>G	p.Ile285Val	missense_variant	5/21	5		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000357 AC: 5 AN: 1400050 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 690498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000371

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000379 AC: 1

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

Oct 30, 2023

The c.853A>G (p.I285V) alteration is located in exon 5 (coding exon 4) of the HMGXB3 gene. This alteration results from a A to G substitution at nucleotide position 853, causing the isoleucine (I) at amino acid position 285 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0038	T;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.97	L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.81	P;.;.
Vest4		0.43
MutPred		0.25		Gain of disorder (P = 0.0745);.;.;
MVP		0.13
ClinPred		0.87	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.25

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

Other links and lift over

dbSNP: rs771950032; hg19: chr5-149391860;