17-44014865-C-A

Variant names:

• chr17-44014865-C-A
• rs2049209908
• NM_032376.4:c.88G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032376.4(TMEM101):​c.88G>T​(p.Gly30Cys) 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. 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: 2.64
• 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]

ENSG00000305936 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2910126).

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.88G>T	p.Gly30Cys	missense	Exon 1 of 4	NP_115752.1	Q96IK0
	TMEM101	NM_001304813.2		c.-38+119G>T		intron	N/A	NP_001291742.1	B4DFS4
	TMEM101	NM_001304814.2		c.-38+119G>T		intron	N/A	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.88G>T	p.Gly30Cys	missense	Exon 1 of 4	ENSP00000206380.3	Q96IK0
	TMEM101	ENST00000589334.5	TSL:5	c.88G>T	p.Gly30Cys	missense	Exon 2 of 5	ENSP00000468025.1	Q96IK0
	TMEM101	ENST00000860792.1		c.88G>T	p.Gly30Cys	missense	Exon 1 of 4	ENSP00000530851.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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	0.17
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.13
Sift	Benign	0.045	D
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.47
MutPred		0.33		Gain of helix (P = 0.062)
MVP		0.40
MPC		1.3
ClinPred		0.92	D
GERP RS		5.7
PromoterAI		-0.098	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
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

Other links and lift over

dbSNP: rs2049209908; hg19: chr17-42092233;