dbSNP rs1168504004: HMGXB4:p.His339Asn (chr22-35265403-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001003681.3(HMGXB4):c.1015C>A(p.His339Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. H339Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HMGXB4
NM_001003681.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.71

Publications

0 publications found

Variant links:

Genes affected

HMGXB4 (HGNC:5003): (HMG-box containing 4) High mobility group (HMG) proteins are nonhistone chromosomal proteins. See HMG2 (MIM 163906) for additional information on HMG proteins.[supplied by OMIM, Nov 2010]

HMGXB4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2515027).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003681.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HMGXB4	NM_001003681.3	MANE Select	c.1015C>A	p.His339Asn	missense	Exon 5 of 11	NP_001003681.1	Q9UGU5
HMGXB4	NM_001362972.2		c.688C>A	p.His230Asn	missense	Exon 4 of 10	NP_001349901.1
HMGXB4	NR_027780.2		n.1263C>A		non_coding_transcript_exon	Exon 6 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HMGXB4	ENST00000216106.6	TSL:5 MANE Select	c.1015C>A	p.His339Asn	missense	Exon 5 of 11	ENSP00000216106.5	Q9UGU5
HMGXB4	ENST00000455359.5	TSL:1	c.688C>A	p.His230Asn	missense	Exon 5 of 5	ENSP00000415500.1	B0QXZ8
HMGXB4	ENST00000418170.5	TSL:1	n.*851C>A		non_coding_transcript_exon	Exon 6 of 12	ENSP00000395532.1	F8WDU7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112002

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0050

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

3.7

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.067

Sift

Pathogenic

0.0

Sift4G

Benign

0.44

Polyphen

0.81

Vest4

0.50

MutPred

0.18

Gain of relative solvent accessibility (P = 0.0098)

MVP

0.59

MPC

0.52

ClinPred

0.97

GERP RS

5.2

Varity_R

0.092

gMVP

0.20

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over