5-150010370-A-G

Variant names:

• chr5-150010370-A-G
• rs1561851416
• NM_014983.3:c.572A>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.572A>G​(p.Glu191Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,399,400 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: 0.0000014 (0 hom.)
• Consequence: HMGXB3 NM_014983.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.57

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=0.17844832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGXB3	NM_014983.3	c.572A>G	p.Glu191Gly	missense_variant	Exon 4 of 20	ENST00000502717.6	NP_055798.3
HMGXB3	XM_047416963.1	c.572A>G	p.Glu191Gly	missense_variant	Exon 4 of 12		XP_047272919.1
HMGXB3	NM_001366501.2	c.313-1885A>G		intron_variant	Intron 3 of 18		NP_001353430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGXB3	ENST00000502717.6	c.572A>G	p.Glu191Gly	missense_variant	Exon 4 of 20	1	NM_014983.3	ENSP00000421917.1
HMGXB3	ENST00000613459.4	c.1310A>G	p.Glu437Gly	missense_variant	Exon 5 of 21	5		ENSP00000479027.1
HMGXB3	ENST00000503427.5	c.572A>G	p.Glu191Gly	missense_variant	Exon 4 of 21	5		ENSP00000422231.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399400 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000560

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

Jan 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.572A>G (p.E191G) 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 572, causing the glutamic acid (E) at amino acid position 191 to be replaced by a glycine (G). 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	0.14
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.90	L;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	.;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0080	.;D;D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.68	P;.;.
Vest4		0.14
MutPred		0.23		Gain of loop (P = 0.0051);.;.;
MVP		0.28
ClinPred		0.89	D
GERP RS		5.9
Varity_R		0.49
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

Other links and lift over

dbSNP: rs1561851416; hg19: chr5-149389933;