rs61755712

Variant names:

• chr15-77458433-C-G
• NM_001304504.2:c.26C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-77458433-C-G
• chr15-77458433-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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]

ACMG classification

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
HMG20A	NM_001304504.2	c.26C>G	p.Thr9Ser	missense_variant	Exon 2 of 10	ENST00000336216.9	NP_001291433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMG20A	ENST00000336216.9	c.26C>G	p.Thr9Ser	missense_variant	Exon 2 of 10	1	NM_001304504.2	ENSP00000336856.4

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;