5-150010303-C-G

Variant names:

• chr5-150010303-C-G
• rs749619104
• NM_014983.3:c.505C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014983.3(HMGXB3):​c.505C>G​(p.Pro169Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,399,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P169S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: HMGXB3 NM_014983.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06543213).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB3	NM_014983.3	MANE Select	c.505C>G	p.Pro169Ala	missense	Exon 4 of 20	NP_055798.3	Q12766
	HMGXB3	NM_001366501.2		c.313-1952C>G		intron	N/A	NP_001353430.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB3	ENST00000502717.6	TSL:1 MANE Select	c.505C>G	p.Pro169Ala	missense	Exon 4 of 20	ENSP00000421917.1	Q12766
	HMGXB3	ENST00000613459.4	TSL:5	c.1243C>G	p.Pro415Ala	missense	Exon 5 of 21	ENSP00000479027.1	A0A8C8PVR7
	HMGXB3	ENST00000971018.1		c.505C>G	p.Pro169Ala	missense	Exon 4 of 21	ENSP00000641077.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000500 AC: 7 AN: 1399478 Hom.: 0 Cov.: 31 AF XY: 0.00000724 AC XY: 5 AN XY: 690246

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000556 AC: 6 AN: 1078992

Other (OTH) AF: 0.0000172 AC: 1 AN: 58016

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	3.7
DANN	Benign	0.97
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.0019
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.041
Sift	Benign	0.32	T
Sift4G	Benign	0.45	T
Polyphen		0.0040	B
Vest4		0.14
MVP		0.072
ClinPred		0.10	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.60
Mutation Taster		=90/10	polymorphism

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: rs749619104; hg19: chr5-149389866;