19-55313037-C-T

Position:

• chr19-55313037-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282011.2(TMEM150B):​c.524G>A​(p.Cys175Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMEM150B NM_001282011.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.368

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]

TMEM150B (HGNC:):

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=0.06871587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM150B	NM_001282011.2	c.524G>A	p.Cys175Tyr	missense_variant	8/8	ENST00000326652.9	NP_001268940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM150B	ENST00000326652.9	c.524G>A	p.Cys175Tyr	missense_variant	8/8	1	NM_001282011.2	ENSP00000320757.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459736 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726114

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Oct 21, 2024

The c.524G>A (p.C175Y) alteration is located in exon 8 (coding exon 6) of the TMEM150B gene. This alteration results from a G to A substitution at nucleotide position 524, causing the cysteine (C) at amino acid position 175 to be replaced by a tyrosine (Y). 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	0.065
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.21
DANN	Benign	0.78
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.26	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.0	N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.1	N;.
REVEL	Benign	0.050
Sift	Benign	1.0	T;.
Sift4G	Benign	0.12	T;.
Polyphen		0.017	B;.
Vest4		0.19
MutPred		0.62		Gain of sheet (P = 0.1208);.;
MVP		0.055
MPC		0.18
ClinPred		0.059	T
GERP RS		0.43
Varity_R		0.044
gMVP		0.29

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: chr19-55824405;