Genetic Variant NM_001114748.2:c.453C>T (chr1-1535428-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001114748.2(TMEM240):c.453C>T(p.Ala151Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,549,496 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 45 hom. )

Consequence

TMEM240
NM_001114748.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.293

Publications

0 publications found

Variant links:

Genes affected

TMEM240 (HGNC:25186): (transmembrane protein 240) This gene encodes a transmembrane-domain containing protein found in the brain and cerebellum. Mutations in this gene result in spinocerebellar ataxia 21. [provided by RefSeq, Dec 2014]

TMEM240 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 21
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Ambry Genetics, PanelApp Australia

TMEM240 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-1535428-G-A is Benign according to our data. Variant chr1-1535428-G-A is described in ClinVar as Benign. ClinVar VariationId is 593226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.293 with no splicing effect.

BS2

High AC in GnomAd4 at 1070 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114748.2. 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
	TMEM240	NM_001114748.2	MANE Select	c.453C>T	p.Ala151Ala	synonymous	Exon 4 of 4	NP_001108220.1	Q5SV17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM240	ENST00000378733.9	TSL:2 MANE Select	c.453C>T	p.Ala151Ala	synonymous	Exon 4 of 4	ENSP00000368007.4	Q5SV17

Frequencies

GnomAD3 genomes

AF:

0.00704

AC:

1070

AN:

151968

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00839

Gnomad OTH

AF:

0.00384

GnomAD2 exomes

AF:

0.00416

AC:

615

AN:

147878

AF XY:

0.00423

show subpopulations

Gnomad AFR exome

AF:

0.00799

Gnomad AMR exome

AF:

0.00298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00347

Gnomad NFE exome

AF:

0.00694

Gnomad OTH exome

AF:

0.00498

GnomAD4 exome

AF:

0.00583

AC:

8141

AN:

1397420

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

3944

AN XY:

689260

show subpopulations

African (AFR)

AF:

0.00894

AC:

282

AN:

31540

American (AMR)

AF:

0.00311

AC:

111

AN:

35676

Ashkenazi Jewish (ASJ)

AF:

0.000119

AC:

AN:

25140

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35710

South Asian (SAS)

AF:

0.00189

AC:

150

AN:

79188

European-Finnish (FIN)

AF:

0.00481

AC:

231

AN:

48022

Middle Eastern (MID)

AF:

0.00193

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00655

AC:

7063

AN:

1078504

Other (OTH)

AF:

0.00499

AC:

289

AN:

57942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

481

962

1444

1925

2406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

244

488

732

976

1220

<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:

0.00704

AC:

1070

AN:

152076

Hom.:

Cov.:

AF XY:

0.00682

AC XY:

507

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00892

AC:

370

AN:

41476

American (AMR)

AF:

0.00458

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.000194

AC:

AN:

5146

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00424

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00837

AC:

569

AN:

67960

Other (OTH)

AF:

0.00380

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

149

198

248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00710

Hom.:

Bravo

AF:

0.00713

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.1

(source)

DANN

Benign

0.66

PhyloP100

-0.29

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

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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