chr2-85599125-C-G

Variant names:

• chr2-85599125-C-G
• NM_001031738.3:c.767G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031738.3(TMEM150A):​c.767G>C​(p.Ser256Thr) 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. 14/22 in silico tools predict a benign 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: 2.89
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24570966).

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.767G>C	p.Ser256Thr	missense	Exon 8 of 8	NP_001026908.1	Q86TG1-1
	TMEM150A	NM_001369917.1		c.767G>C	p.Ser256Thr	missense	Exon 7 of 7	NP_001356846.1	Q86TG1-1
	TMEM150A	NM_153342.4		c.608G>C	p.Ser203Thr	missense	Exon 7 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.767G>C	p.Ser256Thr	missense	Exon 8 of 8	ENSP00000334708.5	Q86TG1-1
	TMEM150A	ENST00000898692.1		c.791G>C	p.Ser264Thr	missense	Exon 8 of 8	ENSP00000568751.1
	TMEM150A	ENST00000409668.1	TSL:2	c.767G>C	p.Ser256Thr	missense	Exon 7 of 7	ENSP00000387292.1	Q86TG1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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	Benign	0.084
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Benign	0.20	T
Sift4G	Benign	0.17	T
Polyphen		0.99	D
Vest4		0.29
MutPred		0.16		Loss of phosphorylation at S256 (P = 0.0392)
MVP		0.57
MPC		0.63
ClinPred		0.69	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.68
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

hg19: chr2-85826248;