1-1535437-G-C

Variant names:

• chr1-1535437-G-C
• NM_001114748.2:c.444C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114748.2(TMEM240):​c.444C>G​(p.Phe148Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F148S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM240 NM_001114748.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09626117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM240	NM_001114748.2	c.444C>G	p.Phe148Leu	missense_variant	Exon 4 of 4	ENST00000378733.9	NP_001108220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM240	ENST00000378733.9	c.444C>G	p.Phe148Leu	missense_variant	Exon 4 of 4	2	NM_001114748.2	ENSP00000368007.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.36
DEOGEN2	Benign	0.37	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.67	.;T
M_CAP	Pathogenic	0.72	D
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.15
Sift	Benign	0.53	T;T
Sift4G	Benign	0.74	T;T
Polyphen		0.0	B;B
Vest4		0.057
MutPred		0.24		Gain of disorder (P = 0.0878);Gain of disorder (P = 0.0878);
MVP		0.030
ClinPred		0.017	T
GERP RS		0.53
Varity_R		0.096
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1470817;