5-150045403-G-A

Position:

• chr5-150045403-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014983.3(HMGXB3):​c.2731-63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,308,540 control chromosomes in the GnomAD database, including 415,227 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 0.83 (53493 hom., cov: 31)
  • Exomes 𝑓: 0.79 (361734 hom.)
• Consequence: HMGXB3 NM_014983.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGXB3	NM_014983.3	c.2731-63G>A		intron_variant		ENST00000502717.6	NP_055798.3
HMGXB3	NM_001366501.2	c.2233-63G>A		intron_variant			NP_001353430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGXB3	ENST00000502717.6	c.2731-63G>A		intron_variant		1	NM_014983.3	ENSP00000421917	P2
HMGXB3	ENST00000503427.5	c.2635-63G>A		intron_variant		5		ENSP00000422231	A2
HMGXB3	ENST00000613459.4	c.3469-63G>A		intron_variant		5		ENSP00000479027	A2
HMGXB3	ENST00000514469.1	c.*285-63G>A		intron_variant, NMD_transcript_variant		5		ENSP00000426631

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126935 AN: 152048 Hom.: 53440 Cov.: 31

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.802

GnomAD4 exome AF: 0.789 AC: 912576 AN: 1156372 Hom.: 361734 AF XY: 0.786 AC XY: 456203 AN XY: 580582

Gnomad4 AFR exome AF: 0.960

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.814

Gnomad4 EAS exome AF: 0.642

Gnomad4 SAS exome AF: 0.697

Gnomad4 FIN exome AF: 0.828

Gnomad4 NFE exome AF: 0.795

Gnomad4 OTH exome AF: 0.795

GnomAD4 genome AF: 0.835 AC: 127043 AN: 152168 Hom.: 53493 Cov.: 31 AF XY: 0.832 AC XY: 61903 AN XY: 74394

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.799

Alfa AF: 0.840 Hom.: 9042

Bravo AF: 0.838

Asia WGS AF: 0.723 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.083
DANN	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2276983; hg19: chr5-149424966; COSMIC: COSV72211493; COSMIC: COSV72211493;