2-85599125-C-G

Position:

• chr2-85599125-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM150A	NM_001031738.3	c.767G>C	p.Ser256Thr	missense_variant	8/8	ENST00000334462.10	NP_001026908.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM150A	ENST00000334462.10	c.767G>C	p.Ser256Thr	missense_variant	8/8	1	NM_001031738.3	ENSP00000334708	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.767G>C (p.S256T) alteration is located in exon 8 (coding exon 7) of the TMEM150A gene. This alteration results from a G to C substitution at nucleotide position 767, causing the serine (S) at amino acid position 256 to be replaced by a threonine (T). 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	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;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	2.0	.;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.29
MutPred		0.16		.;Loss of phosphorylation at S256 (P = 0.0392);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

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: chr2-85826248;