5-150027170-G-T

Variant summary

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

The NM_014983.3(HMGXB3):c.1734+53G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 1,428,946 control chromosomes in the GnomAD database, including 451,240 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 0.80 (49273 hom., cov: 33)
  • Exomes 𝑓: 0.79 (401967 hom.)
• Consequence: HMGXB3 NM_014983.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGXB3	NM_014983.3	c.1734+53G>T		intron_variant		ENST00000502717.6
HMGXB3	NM_001366501.2	c.1236+53G>T		intron_variant
HMGXB3	XM_047416963.1	c.1734+53G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGXB3	ENST00000502717.6	c.1734+53G>T		intron_variant		1	NM_014983.3	P2
HMGXB3	ENST00000503427.5	c.1638+53G>T		intron_variant		5		A2
HMGXB3	ENST00000613459.4	c.2472+53G>T		intron_variant		5		A2
HMGXB3	ENST00000514469.1	c.55+53G>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122229 AN: 152060 Hom.: 49233 Cov.: 33

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.780

GnomAD4 exome AF: 0.792 AC: 1011152 AN: 1276768 Hom.: 401967 AF XY: 0.787 AC XY: 498104 AN XY: 632558

Gnomad4 AFR exome AF: 0.839

Gnomad4 AMR exome AF: 0.778

Gnomad4 ASJ exome AF: 0.820

Gnomad4 EAS exome AF: 0.645

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.836

Gnomad4 NFE exome AF: 0.805

Gnomad4 OTH exome AF: 0.789

GnomAD4 genome AF: 0.804 AC: 122322 AN: 152178 Hom.: 49273 Cov.: 33 AF XY: 0.801 AC XY: 59583 AN XY: 74392

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.775

Alfa AF: 0.797 Hom.: 60678

Bravo AF: 0.802

Asia WGS AF: 0.668 AC: 2328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.6
Dann	Benign	0.44

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: rs2304069; hg19: chr5-149406733; COSMIC: COSV71803339; COSMIC: COSV71803339;