TMEM240 p.Arg142Gly

Variant names:

• chr1-1535457-G-C
• rs763113928
• NM_001114748.2:c.424C>G
• TMEM240 p.Arg142Gly

Your query was ambiguous. Multiple possible variants found:

• chr1-1535457-G-C
• chr1-1535455-CCG-ACC
• chr1-1535455-CCG-GCC
• chr1-1535455-CCG-TCC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001114748.2(TMEM240):​c.424C>G​(p.Arg142Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000859 in 1,396,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R142Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000086 (0 hom.)
• Consequence: TMEM240 NM_001114748.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, Orphanet, G2P, PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.37147334).
• BS2: High AC in GnomAdExome4 at 12 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.424C>G	p.Arg142Gly	missense	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.424C>G	p.Arg142Gly	missense	Exon 4 of 4	ENSP00000368007.4	Q5SV17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000859 AC: 12 AN: 1396934 Hom.: 0 Cov.: 33 AF XY: 0.00000871 AC XY: 6 AN XY: 689008

African (AFR) AF: 0.00 AC: 0 AN: 31524

American (AMR) AF: 0.00 AC: 0 AN: 35648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25122

East Asian (EAS) AF: 0.00 AC: 0 AN: 35686

South Asian (SAS) AF: 0.00 AC: 0 AN: 79140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1078342

Other (OTH) AF: 0.00 AC: 0 AN: 57930

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.66	D
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.087
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.075
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.011	D
Varity_R		0.33
gMVP		0.64
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs763113928;

hg19: chr1-1470837;