Variant 15-77471015-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001304504.2(HMG20A):c.556C>T(p.Arg186Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,506 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HMG20A
NM_001304504.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03

Variant links:

Genes affected

HMG20A (HGNC:5001): (high mobility group 20A) Enables identical protein binding activity. Predicted to be involved in regulation of gene expression. Predicted to act upstream of or within negative regulation of neuron differentiation; negative regulation of protein sumoylation; and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

HMG20A links:

HMG20A (HGNC:):

HMG20A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30338123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMG20A	NM_001304504.2 linkuse as main transcript	c.556C>T	p.Arg186Cys	missense_variant	5/10	ENST00000336216.9	NP_001291433.1	Q9NP66-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HMG20A	ENST00000336216.9 linkuse as main transcript	c.556C>T	p.Arg186Cys	missense_variant	5/10	1	NM_001304504.2	ENSP00000336856.4	Q9NP66-1
HMG20A	ENST00000381714.7 linkuse as main transcript	c.556C>T	p.Arg186Cys	missense_variant	6/11	1		ENSP00000371133.3	Q9NP66-1
HMG20A	ENST00000559035.5 linkuse as main transcript	n.*213C>T		downstream_gene_variant		4		ENSP00000453592.1	H0YMG2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248540

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459506

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726054

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000596

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 04, 2024

The c.556C>T (p.R186C) alteration is located in exon 6 (coding exon 4) of the HMG20A gene. This alteration results from a C to T substitution at nucleotide position 556, causing the arginine (R) at amino acid position 186 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

T;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;D

M_CAP

Benign

0.038

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.33

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-4.1

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.43

MutPred

0.25

Loss of MoRF binding (P = 0.066);Loss of MoRF binding (P = 0.066);

MVP

0.39

MPC

1.3

ClinPred

0.99

GERP RS

5.0

Varity_R

0.51

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over