15-77458433-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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. 15/22 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.74
• Publications: 5 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: Benign. The variant received -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 VariationId is 710819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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>T	p.Thr9Ile	missense	Exon 2 of 10	NP_001291433.1	Q9NP66-1
	HMG20A	NM_018200.4		c.26C>T	p.Thr9Ile	missense	Exon 3 of 11	NP_060670.1	Q9NP66-1
	HMG20A	NM_001304505.2		c.-226C>T		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>T	p.Thr9Ile	missense	Exon 2 of 10	ENSP00000336856.4	Q9NP66-1
	HMG20A	ENST00000381714.7	TSL:1	c.26C>T	p.Thr9Ile	missense	Exon 3 of 11	ENSP00000371133.3	Q9NP66-1
	HMG20A	ENST00000859564.1		c.26C>T	p.Thr9Ile	missense	Exon 2 of 10	ENSP00000529622.1

Frequencies

GnomAD3 genomes AF: 0.00105 AC: 160 AN: 152128 Hom.: 2 Cov.: 32

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

GnomAD2 exomes AF: 0.00105 AC: 263 AN: 251192 AF XY: 0.00100

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 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

African (AFR) AF: 0.000269 AC: 9 AN: 33438

American (AMR) AF: 0.000224 AC: 10 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86236

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53392

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.00185 AC: 2052 AN: 1111336

Other (OTH) AF: 0.00108 AC: 65 AN: 60352

GnomAD4 genome AF: 0.00105 AC: 160 AN: 152246 Hom.: 2 Cov.: 32 AF XY: 0.000914 AC XY: 68 AN XY: 74432

African (AFR) AF: 0.000409 AC: 17 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00151 AC: 103 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00120 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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.015
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.7
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.079	B
Vest4		0.48
MVP		0.62
MPC		0.48
ClinPred		0.046	T
GERP RS		5.8
PromoterAI		-0.086	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.082
gMVP		0.43
Mutation Taster		=97/3	polymorphism

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;