3-50358340-A-C

Position:

• chr3-50358340-A-C

Variant summary

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

The ENST00000266025.4(TMEM115):​c.724T>G​(p.Leu242Val) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM115 ENST00000266025.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.342

Genes affected

TMEM115 (HGNC:30055): (transmembrane protein 115) Enables identical protein binding activity. Involved in retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum. Located in Golgi cisterna membrane and nucleus. Colocalizes with Golgi transport complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272104 (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=0.085541576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM115	NM_007024.5	c.724T>G	p.Leu242Val	missense_variant	1/2	ENST00000266025.4	NP_008955.1
LOC127898564	NR_183066.1	n.498A>C		non_coding_transcript_exon_variant	3/5
CYB561D2	NR_111912.2	n.275+6780A>C		intron_variant
LOC127898564	NR_183067.1	n.389+6294A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM115	ENST00000266025.4	c.724T>G	p.Leu242Val	missense_variant	1/2	1	NM_007024.5	ENSP00000266025.3
ENSG00000272104	ENST00000606589.1	c.127+6780A>C		intron_variant		3		ENSP00000476225.1
CYB561D2	ENST00000490926.1	n.587A>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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 27, 2022

The c.724T>G (p.L242V) alteration is located in exon 1 (coding exon 1) of the TMEM115 gene. This alteration results from a T to G substitution at nucleotide position 724, causing the leucine (L) at amino acid position 242 to be replaced by a valine (V). 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	0.074
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.6
DANN	Benign	0.55
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.63
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.16	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.037
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.22
MutPred		0.33		Gain of sheet (P = 0.0221);
MVP		0.11
MPC		0.68
ClinPred		0.62	D
GERP RS		0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-50395771;