Variant 1-1535427-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001114748.2(TMEM240):c.454G>A(p.Ala152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,549,654 control chromosomes in the GnomAD database, including 1,069 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 98 hom., cov: 32)

Exomes 𝑓: 0.034 ( 971 hom. )

Consequence

TMEM240
NM_001114748.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.301

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001060605).

BP6

Variant 1-1535427-C-T is Benign according to our data. Variant chr1-1535427-C-T is described in ClinVar as [Benign]. Clinvar id is 1235425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0258 (3925/152222) while in subpopulation NFE AF= 0.0325 (2212/67990). AF 95% confidence interval is 0.0314. There are 98 homozygotes in gnomad4. There are 2059 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3925 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM240	NM_001114748.2 linkuse as main transcript	c.454G>A	p.Ala152Thr	missense_variant	4/4	ENST00000378733.9	NP_001108220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM240	ENST00000378733.9 linkuse as main transcript	c.454G>A	p.Ala152Thr	missense_variant	4/4	2	NM_001114748.2	ENSP00000368007	P1

Frequencies

GnomAD3 genomes

AF:

0.0258

AC:

3924

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00625

Gnomad AMI

AF:

0.0890

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.0541

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0774

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0320

AC:

4734

AN:

147844

Hom.:

122

AF XY:

0.0329

AC XY:

2594

AN XY:

78960

show subpopulations

Gnomad AFR exome

AF:

0.00386

Gnomad AMR exome

AF:

0.00882

Gnomad ASJ exome

AF:

0.0518

Gnomad EAS exome

AF:

0.000185

Gnomad SAS exome

AF:

0.0355

Gnomad FIN exome

AF:

0.0753

Gnomad NFE exome

AF:

0.0350

Gnomad OTH exome

AF:

0.0313

GnomAD4 exome

AF:

0.0345

AC:

48205

AN:

1397432

Hom.:

971

Cov.:

AF XY:

0.0345

AC XY:

23776

AN XY:

689266

show subpopulations

Gnomad4 AFR exome

AF:

0.00498

Gnomad4 AMR exome

AF:

0.00905

Gnomad4 ASJ exome

AF:

0.0531

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.0370

Gnomad4 FIN exome

AF:

0.0701

Gnomad4 NFE exome

AF:

0.0353

Gnomad4 OTH exome

AF:

0.0318

GnomAD4 genome

AF:

0.0258

AC:

3925

AN:

152222

Hom.:

Cov.:

AF XY:

0.0277

AC XY:

2059

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00623

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.0541

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0323

Gnomad4 FIN

AF:

0.0774

Gnomad4 NFE

AF:

0.0325

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0308

Hom.:

Bravo

AF:

0.0209

TwinsUK

AF:

0.0334

AC:

124

ALSPAC

AF:

0.0397

AC:

153

ExAC

AF:

0.0333

AC:

832

Asia WGS

AF:

0.0140

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.27

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.77

.;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.040

Sift

Benign

0.62

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.014

B;B

Vest4

0.023

ClinPred

0.00096

GERP RS

-0.46

Varity_R

0.038

gMVP

0.27

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