2-85599997-C-A

Variant names:

• chr2-85599997-C-A
• NM_001031738.3:c.290G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001031738.3(TMEM150A):​c.290G>T​(p.Arg97Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM150A NM_001031738.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80

Genes affected

TMEM150A (HGNC:24677): (transmembrane protein 150A) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM150A	NM_001031738.3	c.290G>T	p.Arg97Leu	missense_variant	Exon 6 of 8	ENST00000334462.10	NP_001026908.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM150A	ENST00000334462.10	c.290G>T	p.Arg97Leu	missense_variant	Exon 6 of 8	1	NM_001031738.3	ENSP00000334708.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.290G>T (p.R97L) alteration is located in exon 6 (coding exon 5) of the TMEM150A gene. This alteration results from a G to T substitution at nucleotide position 290, causing the arginine (R) at amino acid position 97 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.83	.;D;D;.
Eigen	Benign	0.065
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;.;T;T
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.2	.;M;M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.4	D;D;D;D
REVEL	Uncertain	0.30
Sift	Benign	0.033	D;T;T;T
Sift4G	Benign	0.061	T;D;D;T
Polyphen		0.0030	B;B;B;.
Vest4		0.43
MutPred		0.84		.;Loss of catalytic residue at R97 (P = 0.0269);Loss of catalytic residue at R97 (P = 0.0269);.;
MVP		0.63
MPC		0.68
ClinPred		0.99	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr2-85827120; COSMIC: COSV57818021; COSMIC: COSV57818021;