NM_003483.6:c.*3092C>T

Variant names:

• chr12-65966384-C-T
• rs7970350
• NM_003483.6:c.*3092C>T

Variant summary

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

The NM_003483.6(HMGA2):​c.*3092C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 173,088 control chromosomes in the GnomAD database, including 22,691 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 0.49 (19260 hom., cov: 32)
  • Exomes 𝑓: 0.56 (3431 hom.)
• Consequence: HMGA2 NM_003483.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789

Genes affected

HMGA2 (HGNC:5009): (high mobility group AT-hook 2) This gene encodes a protein that belongs to the non-histone chromosomal high mobility group (HMG) protein family. HMG proteins function as architectural factors and are essential components of the enhancesome. This protein contains structural DNA-binding domains and may act as a transcriptional regulating factor. Identification of the deletion, amplification, and rearrangement of this gene that are associated with myxoid liposarcoma suggests a role in adipogenesis and mesenchymal differentiation. A gene knock out study of the mouse counterpart demonstrated that this gene is involved in diet-induced obesity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGA2	NM_003483.6	c.*3092C>T		downstream_gene_variant		ENST00000403681.7	NP_003474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000403681.7	c.*3092C>T		downstream_gene_variant		1	NM_003483.6	ENSP00000384026.2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74826 AN: 151916 Hom.: 19265 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.560 AC: 11783 AN: 21054 Hom.: 3431 AF XY: 0.561 AC XY: 5492 AN XY: 9788

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.731

Gnomad4 SAS exome AF: 0.713

Gnomad4 FIN exome AF: 0.498

Gnomad4 NFE exome AF: 0.505

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.492 AC: 74840 AN: 152034 Hom.: 19260 Cov.: 32 AF XY: 0.500 AC XY: 37122 AN XY: 74302

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.524

Alfa AF: 0.461 Hom.: 2438

Bravo AF: 0.499

Asia WGS AF: 0.679 AC: 2358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.91
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7970350; hg19: chr12-66360164;