15-77470943-C-T

Variant names:

• chr15-77470943-C-T
• rs1044909978
• NM_001304504.2:c.484C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001304504.2(HMG20A):​c.484C>T​(p.Arg162Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 14/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HMG20A NM_001304504.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.902

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.484C>T	p.Arg162Cys	missense	Exon 5 of 10	NP_001291433.1	Q9NP66-1
	HMG20A	NM_018200.4		c.484C>T	p.Arg162Cys	missense	Exon 6 of 11	NP_060670.1	Q9NP66-1
	HMG20A	NM_001304505.2		c.145C>T	p.Arg49Cys	missense	Exon 5 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.484C>T	p.Arg162Cys	missense	Exon 5 of 10	ENSP00000336856.4	Q9NP66-1
	HMG20A	ENST00000381714.7	TSL:1	c.484C>T	p.Arg162Cys	missense	Exon 6 of 11	ENSP00000371133.3	Q9NP66-1
	HMG20A	ENST00000859564.1		c.484C>T	p.Arg162Cys	missense	Exon 5 of 10	ENSP00000529622.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.85	D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Pathogenic	0.42	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		7.6
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.48		Loss of MoRF binding (P = 0.0443)
MVP		0.93
MPC		1.5
ClinPred		1.0	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.65
Mutation Taster		=7/93	disease causing

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: rs1044909978; hg19: chr15-77763285; COSMIC: COSV60312424; COSMIC: COSV60312424;