15-77458433-C-G

Variant names:

• chr15-77458433-C-G
• rs61755712
• NM_001304504.2:c.26C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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
• Publications: 0 publications found

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]

ENSG00000294779 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304504.2. 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
	HMG20A	NM_001304504.2	MANE Select	c.26C>G	p.Thr9Ser	missense	Exon 2 of 10	NP_001291433.1	Q9NP66-1
	HMG20A	NM_018200.4		c.26C>G	p.Thr9Ser	missense	Exon 3 of 11	NP_060670.1	Q9NP66-1
	HMG20A	NM_001304505.2		c.-226C>G		5_prime_UTR	Exon 2 of 10	NP_001291434.1	B4DMG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMG20A	ENST00000336216.9	TSL:1 MANE Select	c.26C>G	p.Thr9Ser	missense	Exon 2 of 10	ENSP00000336856.4	Q9NP66-1
	HMG20A	ENST00000381714.7	TSL:1	c.26C>G	p.Thr9Ser	missense	Exon 3 of 11	ENSP00000371133.3	Q9NP66-1
	HMG20A	ENST00000859564.1		c.26C>G	p.Thr9Ser	missense	Exon 2 of 10	ENSP00000529622.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.098
Sift	Benign	0.14	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.12		Loss of glycosylation at S8 (P = 0.0731)
MVP		0.54
MPC		0.39
ClinPred		0.15	T
GERP RS		5.8
PromoterAI		-0.047	Neutral
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

Other links and lift over

dbSNP: rs61755712; hg19: chr15-77750775;