chr17-44011984-G-A

Position:

• chr17-44011984-G-A

Variant summary

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

The NM_032376.4(TMEM101):​c.718C>T​(p.Leu240Phe) 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. 12/20 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: TMEM101 NM_032376.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

Genes affected

TMEM101 (HGNC:28653): (transmembrane protein 101) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. Predicted to be integral component of 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=0.14935794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM101	NM_032376.4	c.718C>T	p.Leu240Phe	missense_variant	4/4	ENST00000206380.8	NP_115752.1
TMEM101	NM_001304813.2	c.544C>T	p.Leu182Phe	missense_variant	5/5		NP_001291742.1
TMEM101	NM_001304814.2	c.544C>T	p.Leu182Phe	missense_variant	5/5		NP_001291743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM101	ENST00000206380.8	c.718C>T	p.Leu240Phe	missense_variant	4/4	1	NM_032376.4	ENSP00000206380.3
TMEM101	ENST00000589334.5	c.718C>T	p.Leu240Phe	missense_variant	5/5	5		ENSP00000468025.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Feb 28, 2023

The c.718C>T (p.L240F) alteration is located in exon 4 (coding exon 4) of the TMEM101 gene. This alteration results from a C to T substitution at nucleotide position 718, causing the leucine (L) at amino acid position 240 to be replaced by a phenylalanine (F). 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	0.19
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T;T
Eigen	Benign	-0.063
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Benign	0.062
Sift	Benign	0.043	.;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.13	B;B
Vest4		0.31
MutPred		0.22		Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);
MVP		0.16
MPC		0.50
ClinPred		0.88	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.62

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: chr17-42089352;