5-150041939-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014983.3(HMGXB3):c.2700A>G(p.Glu900=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,551,208 control chromosomes in the GnomAD database, including 24,784 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (8420 hom., cov: 32)
  • Exomes 𝑓: 0.13 (16364 hom.)
• Consequence: HMGXB3 NM_014983.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGXB3	NM_014983.3	c.2700A>G	p.Glu900=	synonymous_variant	15/20	ENST00000502717.6
HMGXB3	NM_001366501.2	c.2202A>G	p.Glu734=	synonymous_variant	14/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGXB3	ENST00000502717.6	c.2700A>G	p.Glu900=	synonymous_variant	15/20	1	NM_014983.3	P2
HMGXB3	ENST00000613459.4	c.3438A>G	p.Glu1146=	synonymous_variant	16/21	5		A2
HMGXB3	ENST00000503427.5	c.2604A>G	p.Glu868=	synonymous_variant	16/21	5		A2
HMGXB3	ENST00000514469.1	c.*254A>G		3_prime_UTR_variant, NMD_transcript_variant	5/7	5

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39190 AN: 151974 Hom.: 8394 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.167 AC: 26091 AN: 156460 Hom.: 3645 AF XY: 0.149 AC XY: 12367 AN XY: 82914

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.0513

Gnomad FIN exome AF: 0.0973

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.126 AC: 176146 AN: 1399116 Hom.: 16364 Cov.: 32 AF XY: 0.122 AC XY: 83848 AN XY: 690080

Gnomad4 AFR exome AF: 0.595

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.0909

Gnomad4 SAS exome AF: 0.0514

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.258 AC: 39260 AN: 152092 Hom.: 8420 Cov.: 32 AF XY: 0.254 AC XY: 18905 AN XY: 74370

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0484

Gnomad4 FIN AF: 0.0902

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.241

Alfa AF: 0.145 Hom.: 3381

Bravo AF: 0.292

Asia WGS AF: 0.125 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	8.5
Dann	Benign	0.60

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: rs2276982; hg19: chr5-149421502; COSMIC: COSV72211670; COSMIC: COSV72211670;