17-44011984-G-A

Variant names:

• chr17-44011984-G-A
• NM_032376.4:c.718C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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: 33)
• Consequence: TMEM101 NM_032376.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14935794).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032376.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM101	NM_032376.4	MANE Select	c.718C>T	p.Leu240Phe	missense	Exon 4 of 4	NP_115752.1	Q96IK0
	TMEM101	NM_001304813.2		c.544C>T	p.Leu182Phe	missense	Exon 5 of 5	NP_001291742.1	B4DFS4
	TMEM101	NM_001304814.2		c.544C>T	p.Leu182Phe	missense	Exon 5 of 5	NP_001291743.1	B4DFS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM101	ENST00000206380.8	TSL:1 MANE Select	c.718C>T	p.Leu240Phe	missense	Exon 4 of 4	ENSP00000206380.3	Q96IK0
	TMEM101	ENST00000589334.5	TSL:5	c.718C>T	p.Leu240Phe	missense	Exon 5 of 5	ENSP00000468025.1	Q96IK0
	TMEM101	ENST00000860792.1		c.691C>T	p.Leu231Phe	missense	Exon 4 of 4	ENSP00000530851.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.062
Sift	Benign	0.043	D
Sift4G	Uncertain	0.038	D
Polyphen		0.13	B
Vest4		0.31
MutPred		0.22		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

Other links and lift over

hg19: chr17-42089352;