rs730880228

Variant names:

• chr12-98516115-C-G
• rs730880228
• NM_001032283.3:c.248C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-98516115-C-G
• chr12-98516115-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003276.2(TMPO):​c.248C>G​(p.Ala83Gly) 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. 14/22 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. A83V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMPO NM_003276.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 1 publications found

Genes affected

TMPO (HGNC:11875): (thymopoietin) Through alternative splicing, this gene encodes several distinct LEM domain containing protein isoforms. LEM domain proteins include inner nuclear membrane and intranuclear proteins, and are involved in a variety of cellular functions including gene expression, chromatin organization, and replication and cell cycle control. The encoded alpha isoform is broadly diffuse in the nucleus and contains a lamin binding domain, while the beta and gamma isoforms are localized to the nuclear membrane and contain an HDAC3 interaction domain. The distinct isoforms may compete with each other when acting to chaperone other proteins and regulate transcription. [provided by RefSeq, Aug 2019]

TMPO-AS1 (HGNC:44158): (TMPO antisense RNA 1)

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=0.13287085).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003276.2. 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
	TMPO	NM_001032283.3	MANE Select	c.248C>G	p.Ala83Gly	missense	Exon 1 of 9	NP_001027454.1
	TMPO	NM_003276.2		c.248C>G	p.Ala83Gly	missense	Exon 1 of 4	NP_003267.1
	TMPO	NM_001307975.2		c.248C>G	p.Ala83Gly	missense	Exon 1 of 8	NP_001294904.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPO	ENST00000556029.6	TSL:1 MANE Select	c.248C>G	p.Ala83Gly	missense	Exon 1 of 9	ENSP00000450627.1
	TMPO	ENST00000266732.8	TSL:1	c.248C>G	p.Ala83Gly	missense	Exon 1 of 4	ENSP00000266732.4
	TMPO	ENST00000393053.6	TSL:1	c.248C>G	p.Ala83Gly	missense	Exon 1 of 6	ENSP00000376773.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.43
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.032
Sift	Benign	0.55	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.27		Gain of catalytic residue at S87 (P = 4e-04)
MVP		0.27
MPC		0.068
ClinPred		0.056	T
GERP RS		1.8
PromoterAI		-0.028	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.2
Varity_R		0.050
gMVP		0.10
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: rs730880228; hg19: chr12-98909893;