rs61755712

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001304504.2(HMG20A):​c.26C>G​(p.Thr9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. T9I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

HMG20A
NM_001304504.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06953925).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HMG20ANM_001304504.2 linkc.26C>G p.Thr9Ser missense_variant Exon 2 of 10 ENST00000336216.9 NP_001291433.1 Q9NP66-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HMG20AENST00000336216.9 linkc.26C>G p.Thr9Ser missense_variant Exon 2 of 10 1 NM_001304504.2 ENSP00000336856.4 Q9NP66-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
13
DANN
Benign
0.85
DEOGEN2
Benign
0.031
T;T;T;T;T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.65
T;.;T;T;T
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.070
T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.20
.;N;N;.;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.8
N;N;N;N;N
REVEL
Benign
0.098
Sift
Benign
0.14
T;T;T;T;T
Sift4G
Benign
0.29
T;T;T;T;T
Polyphen
0.0
.;B;B;.;.
Vest4
0.28, 0.28
MutPred
0.12
Loss of glycosylation at S8 (P = 0.0731);Loss of glycosylation at S8 (P = 0.0731);Loss of glycosylation at S8 (P = 0.0731);Loss of glycosylation at S8 (P = 0.0731);Loss of glycosylation at S8 (P = 0.0731);
MVP
0.54
MPC
0.39
ClinPred
0.15
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.081
gMVP
0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-77750775; API