Genetic Variant NM_006339.3:c.740C>G (chr19-3577039-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006339.3(HMG20B):c.740C>G(p.Ala247Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 1,548,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HMG20B
NM_006339.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

Publications

0 publications found

Variant links:

Genes affected

HMG20B (HGNC:5002): (high mobility group 20B) Predicted to enable DNA binding activity. Predicted to be involved in regulation of gene expression. Predicted to act upstream of or within negative regulation of protein sumoylation; positive regulation of neuron differentiation; and skeletal muscle cell differentiation. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

HMG20B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33129033).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006339.3. 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
	HMG20B	NM_006339.3	MANE Select	c.740C>G	p.Ala247Gly	missense	Exon 8 of 10	NP_006330.2	Q9P0W2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HMG20B	ENST00000333651.11	TSL:1 MANE Select	c.740C>G	p.Ala247Gly	missense	Exon 8 of 10	ENSP00000328269.6	Q9P0W2-1
HMG20B	ENST00000488973.6	TSL:1	n.1653C>G		non_coding_transcript_exon	Exon 6 of 8
HMG20B	ENST00000888792.1		c.740C>G	p.Ala247Gly	missense	Exon 8 of 10	ENSP00000558851.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1396810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689116

show subpopulations

African (AFR)

AF:

0.0000633

AC:

AN:

31588

American (AMR)

AF:

0.00

AC:

AN:

35778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25144

East Asian (EAS)

AF:

0.00

AC:

AN:

35828

South Asian (SAS)

AF:

0.00

AC:

AN:

79202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4500

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079522

Other (OTH)

AF:

0.00

AC:

AN:

57868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67944

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

0.16

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.2

PhyloP100

1.3

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.15

Sift

Benign

0.047

Sift4G

Benign

0.21

Polyphen

0.89

Vest4

0.33

MutPred

0.23

Gain of loop (P = 0.0121)

MVP

0.67

MPC

1.7

ClinPred

0.89

GERP RS

4.0

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.29

gMVP

0.49

Mutation Taster

=91/9

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over