5-150000930-G-A

Variant names:

• chr5-150000930-G-A
• rs4705403
• NM_014983.3:c.-252G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014983.3(HMGXB3):​c.-252G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 154,684 control chromosomes in the GnomAD database, including 1,341 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 0.12 (1297 hom., cov: 32)
  • Exomes 𝑓: 0.15 (44 hom.)
• Consequence: HMGXB3 NM_014983.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• Publications: 12 publications found

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]

HMGXB3 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015045702).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014983.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB3	NM_014983.3	MANE Select	c.-252G>A		5_prime_UTR	Exon 1 of 20	NP_055798.3
	HMGXB3	NM_001366501.2		c.-252G>A		5_prime_UTR	Exon 1 of 19	NP_001353430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB3	ENST00000502717.6	TSL:1 MANE Select	c.-252G>A		5_prime_UTR	Exon 1 of 20	ENSP00000421917.1
	HMGXB3	ENST00000613459.4	TSL:5	c.487G>A	p.Glu163Lys	missense	Exon 2 of 21	ENSP00000479027.1
	HMGXB3	ENST00000503427.5	TSL:5	c.-252G>A		5_prime_UTR	Exon 1 of 21	ENSP00000422231.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18033 AN: 151948 Hom.: 1298 Cov.: 32

Gnomad AFR AF: 0.0983

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0396

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.151 AC: 396 AN: 2618 Hom.: 44 Cov.: 0 AF XY: 0.133 AC XY: 179 AN XY: 1344

African (AFR) AF: 0.135 AC: 10 AN: 74

American (AMR) AF: 0.125 AC: 1 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.0426 AC: 4 AN: 94

European-Finnish (FIN) AF: 0.0972 AC: 41 AN: 422

Middle Eastern (MID) AF: 0.186 AC: 302 AN: 1620

European-Non Finnish (NFE) AF: 0.118 AC: 24 AN: 204

Other (OTH) AF: 0.0729 AC: 14 AN: 192

GnomAD4 genome AF: 0.119 AC: 18035 AN: 152066 Hom.: 1297 Cov.: 32 AF XY: 0.119 AC XY: 8865 AN XY: 74326

African (AFR) AF: 0.0982 AC: 4075 AN: 41502

American (AMR) AF: 0.260 AC: 3967 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3470

East Asian (EAS) AF: 0.101 AC: 521 AN: 5138

South Asian (SAS) AF: 0.0392 AC: 189 AN: 4820

European-Finnish (FIN) AF: 0.0893 AC: 947 AN: 10604

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7388 AN: 67938

Other (OTH) AF: 0.139 AC: 293 AN: 2112

Alfa AF: 0.119 Hom.: 2020

Bravo AF: 0.133

TwinsUK AF: 0.113 AC: 420

ALSPAC AF: 0.0976 AC: 376

Asia WGS AF: 0.0820 AC: 287 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.0031	T
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0015	T
PhyloP100		0.26
Sift4G	Benign	0.20	T
Vest4		0.10
MVP		0.32
GERP RS		0.20
PromoterAI		0.062	Neutral
Varity_R		0.033
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4705403; hg19: chr5-149380493; COSMIC: COSV57060948; COSMIC: COSV57060948;