chr17-44012065-G-C

Variant names:

• chr17-44012065-G-C
• rs2049166164
• NM_032376.4:c.637C>G

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.637C>G​(p.Pro213Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 4.83
• 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=0.1315588).

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.637C>G	p.Pro213Ala	missense	Exon 4 of 4	NP_115752.1	Q96IK0
	TMEM101	NM_001304813.2		c.463C>G	p.Pro155Ala	missense	Exon 5 of 5	NP_001291742.1	B4DFS4
	TMEM101	NM_001304814.2		c.463C>G	p.Pro155Ala	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.637C>G	p.Pro213Ala	missense	Exon 4 of 4	ENSP00000206380.3	Q96IK0
	TMEM101	ENST00000589334.5	TSL:5	c.637C>G	p.Pro213Ala	missense	Exon 5 of 5	ENSP00000468025.1	Q96IK0
	TMEM101	ENST00000860792.1		c.610C>G	p.Pro204Ala	missense	Exon 4 of 4	ENSP00000530851.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.072
PhyloP100		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.049
gMVP		0.52

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2049166164; hg19: chr17-42089433;