15-77458433-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001304504.2(HMG20A):​c.26C>T​(p.Thr9Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,613,254 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

HMG20A
NM_001304504.2 missense

Scores

3
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0046669245).
BP6
Variant 15-77458433-C-T is Benign according to our data. Variant chr15-77458433-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 710819.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HMG20ANM_001304504.2 linkc.26C>T p.Thr9Ile 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>T p.Thr9Ile missense_variant Exon 2 of 10 1 NM_001304504.2 ENSP00000336856.4 Q9NP66-1

Frequencies

GnomAD3 genomes
AF:
0.00105
AC:
160
AN:
152128
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.0428
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:
0.00316
Gnomad NFE
AF:
0.00151
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00105
AC:
263
AN:
251192
Hom.:
3
AF XY:
0.00100
AC XY:
136
AN XY:
135754
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000203
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00216
Gnomad OTH exome
AF:
0.000979
GnomAD4 exome
AF:
0.00147
AC:
2148
AN:
1461008
Hom.:
5
Cov.:
29
AF XY:
0.00142
AC XY:
1034
AN XY:
726826
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.00185
Gnomad4 OTH exome
AF:
0.00108
GnomAD4 genome
AF:
0.00105
AC:
160
AN:
152246
Hom.:
2
Cov.:
32
AF XY:
0.000914
AC XY:
68
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00151
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00119
Hom.:
0
Bravo
AF:
0.00127
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.00285
AC:
11
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00233
AC:
20
ExAC
AF:
0.00129
AC:
157
EpiCase
AF:
0.00164
EpiControl
AF:
0.00154

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 02, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
15
DANN
Benign
0.87
DEOGEN2
Benign
0.077
T;T;T;T;T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.015
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.85
T;.;T;T;D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.0047
T;T;T;T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
0.55
.;N;N;.;.
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.1
D;N;N;N;N
REVEL
Benign
0.18
Sift
Uncertain
0.0030
D;D;D;D;D
Sift4G
Uncertain
0.0090
D;T;T;D;D
Polyphen
0.079
.;B;B;.;.
Vest4
0.48, 0.51
MVP
0.62
MPC
0.48
ClinPred
0.046
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.082
gMVP
0.43

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

LitVar

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

Other links and lift over

dbSNP: rs61755712; hg19: chr15-77750775; API