rs727504659

Variant names:

• chr12-98516119-G-A
• rs727504659
• NM_001032283.3:c.252G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-98516119-G-A
• chr12-98516119-G-C
• chr12-98516119-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001032283.3(TMPO):​c.252G>A​(p.Ala84Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A84A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMPO NM_001032283.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.390
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 12-98516119-G-A is Benign according to our data. Variant chr12-98516119-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1792667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.39 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032283.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPO	NM_001032283.3	MANE Select	c.252G>A	p.Ala84Ala	synonymous	Exon 1 of 9	NP_001027454.1
	TMPO	NM_003276.2		c.252G>A	p.Ala84Ala	synonymous	Exon 1 of 4	NP_003267.1
	TMPO	NM_001307975.2		c.252G>A	p.Ala84Ala	synonymous	Exon 1 of 8	NP_001294904.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPO	ENST00000556029.6	TSL:1 MANE Select	c.252G>A	p.Ala84Ala	synonymous	Exon 1 of 9	ENSP00000450627.1
	TMPO	ENST00000266732.8	TSL:1	c.252G>A	p.Ala84Ala	synonymous	Exon 1 of 4	ENSP00000266732.4
	TMPO	ENST00000393053.6	TSL:1	c.252G>A	p.Ala84Ala	synonymous	Exon 1 of 6	ENSP00000376773.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

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: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 114640 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1357218 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 669482

African (AFR) AF: 0.00 AC: 0 AN: 28420

American (AMR) AF: 0.00 AC: 0 AN: 27570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22330

East Asian (EAS) AF: 0.00 AC: 0 AN: 34802

South Asian (SAS) AF: 0.00 AC: 0 AN: 74628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5036

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071066

Other (OTH) AF: 0.00 AC: 0 AN: 56216

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.96
PhyloP100		-0.39
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.8

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: rs727504659; hg19: chr12-98909897;