NM_025075.4:c.18C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_025075.4(THOC7):c.18C>T(p.Asp6Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,252,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

THOC7
NM_025075.4 splice_region, synonymous

Scores

Splicing: ADA: 0.004725

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.168

Publications

0 publications found

Variant links:

Genes affected

THOC7 (HGNC:29874): (THO complex subunit 7) Predicted to enable RNA binding activity. Involved in mRNA export from nucleus and viral mRNA export from host cell nucleus. Located in cytosol and nuclear speck. Part of THO complex part of transcription export complex. Colocalizes with chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]

THOC7 links:

ATXN7 (HGNC:10560): (ataxin 7) The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the 'pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. This locus has been mapped to chromosome 3, and it has been determined that the diseased allele associated with spinocerebellar ataxia-7 contains 37-306 CAG repeats (near the N-terminus), compared to 4-35 in the normal allele. The encoded protein is a component of the SPT3/TAF9/GCN5 acetyltransferase (STAGA) and TBP-free TAF-containing (TFTC) chromatin remodeling complexes, and it thus plays a role in transcriptional regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ATXN7 Gene-Disease associations (from GenCC):

spinocerebellar ataxia 7
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
spinocerebellar ataxia type 7
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

ATXN7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=-0.61).

BP7

Synonymous conserved (PhyloP=-0.168 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025075.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
THOC7	NM_025075.4	MANE Select	c.18C>T	p.Asp6Asp	splice_region synonymous	Exon 1 of 8	NP_079351.2	Q6I9Y2
THOC7	NM_001285387.3		c.-21C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_001272316.1	A0A5S6STF9
THOC7	NM_001285404.2		c.-407C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001272333.1	A0A5S6STF9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
THOC7	ENST00000295899.10	TSL:1 MANE Select	c.18C>T	p.Asp6Asp	splice_region synonymous	Exon 1 of 8	ENSP00000295899.5	Q6I9Y2
THOC7	ENST00000469584.5	TSL:2	c.-21C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000418518.2	A0A5S6STF9
THOC7	ENST00000464327.2	TSL:5	c.-253C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000419443.2	F8WF22

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000236

AC:

AN:

1100596

Hom.:

Cov.:

AF XY:

0.0000246

AC XY:

AN XY:

527710

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22840

American (AMR)

AF:

0.00

AC:

AN:

8354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14090

East Asian (EAS)

AF:

0.00

AC:

AN:

26714

South Asian (SAS)

AF:

0.00

AC:

AN:

21760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2940

European-Non Finnish (NFE)

AF:

0.0000277

AC:

AN:

938270

Other (OTH)

AF:

0.00

AC:

AN:

44240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151616

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74042

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41360

American (AMR)

AF:

0.00

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67858

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

-0.17

PromoterAI

-0.069

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0047

dbscSNV1_RF

Benign

0.090

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over