2-85599997-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031738.3. 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
	TMEM150A	NM_001031738.3	MANE Select	c.290G>T	p.Arg97Leu	missense	Exon 6 of 8	NP_001026908.1	Q86TG1-1
	TMEM150A	NM_001369917.1		c.290G>T	p.Arg97Leu	missense	Exon 5 of 7	NP_001356846.1	Q86TG1-1
	TMEM150A	NM_153342.4		c.131G>T	p.Arg44Leu	missense	Exon 5 of 7	NP_699173.2	Q86TG1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM150A	ENST00000334462.10	TSL:1 MANE Select	c.290G>T	p.Arg97Leu	missense	Exon 6 of 8	ENSP00000334708.5	Q86TG1-1
	TMEM150A	ENST00000898692.1		c.314G>T	p.Arg105Leu	missense	Exon 6 of 8	ENSP00000568751.1
	TMEM150A	ENST00000409668.1	TSL:2	c.290G>T	p.Arg97Leu	missense	Exon 5 of 7	ENSP00000387292.1	Q86TG1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.065
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		3.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.30
Sift	Benign	0.033	D
Sift4G	Benign	0.061	T
Polyphen		0.0030	B
Vest4		0.43
MutPred		0.84		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
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

hg19: chr2-85827120; COSMIC: COSV57818021; COSMIC: COSV57818021;