19-55313029-G-C

Position:

• chr19-55313029-G-C

Variant summary

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

The NM_001282011.2(TMEM150B):​c.532C>G​(p.Arg178Gly) 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: 33)
• Consequence: TMEM150B NM_001282011.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68

Genes affected

TMEM150B (HGNC:34415): (transmembrane protein 150B) This gene encodes a protein that belongs to the DRAM (damage-regulated autophagy modulator) family of membrane-spanning proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

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, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM150B	NM_001282011.2	c.532C>G	p.Arg178Gly	missense_variant	8/8	ENST00000326652.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM150B	ENST00000326652.9	c.532C>G	p.Arg178Gly	missense_variant	8/8	1	NM_001282011.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Nov 30, 2022

The c.532C>G (p.R178G) alteration is located in exon 8 (coding exon 6) of the TMEM150B gene. This alteration results from a C to G substitution at nucleotide position 532, causing the arginine (R) at amino acid position 178 to be replaced by a glycine (G). 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	0.29
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.064	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.1	N;.
REVEL	Benign	0.29
Sift	Benign	0.052	T;.
Sift4G	Uncertain	0.043	D;.
Polyphen		0.95	P;.
Vest4		0.78
MutPred		0.64		Gain of helix (P = 0.0199);.;
MVP		0.34
MPC		0.55
ClinPred		0.90	D
GERP RS		4.5
Varity_R		0.42
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs770579254; hg19: chr19-55824397;