Genetic Variant TMEM240:p.Ala151Ala (chr1-1535428-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 593226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-1535428-G-A is described in Lovd as [Likely_benign].

BP7

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

BS2

High AC in GnomAd4 at 1070 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM240	NM_001114748.2 link	c.453C>T	p.Ala151Ala	synonymous_variant	Exon 4 of 4	ENST00000378733.9	NP_001108220.1	Q5SV17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM240	ENST00000378733.9 link	c.453C>T	p.Ala151Ala	synonymous_variant	Exon 4 of 4	2	NM_001114748.2	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

GnomAD3 exomes

AF:

0.00416

AC:

615

AN:

147878

Hom.:

AF XY:

0.00423

AC XY:

334

AN XY:

78988

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 SAS exome

AF:

0.00146

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

Gnomad4 AFR exome

AF:

0.00894

Gnomad4 AMR exome

AF:

0.00311

Gnomad4 ASJ exome

AF:

0.000119

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00189

Gnomad4 FIN exome

AF:

0.00481

Gnomad4 NFE exome

AF:

0.00655

Gnomad4 OTH exome

AF:

0.00499

GnomAD4 genome

AF:

0.00704

AC:

1070

AN:

152076

Hom.:

Cov.:

AF XY:

0.00682

AC XY:

507

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00892

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.00837

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00710

Hom.:

Bravo

AF:

0.00713

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TMEM240: BP4, BP7, BS1, BS2 -

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 01, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.1

DANN

Benign

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over