17-44014865-C-A

Position:

• chr17-44014865-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM101	NM_032376.4	c.88G>T	p.Gly30Cys	missense_variant	1/4	ENST00000206380.8	NP_115752.1
TMEM101	NM_001304813.2	c.-38+119G>T		intron_variant			NP_001291742.1
TMEM101	NM_001304814.2	c.-38+119G>T		intron_variant			NP_001291743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM101	ENST00000206380.8	c.88G>T	p.Gly30Cys	missense_variant	1/4	1	NM_032376.4	ENSP00000206380.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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 06, 2021

The c.88G>T (p.G30C) alteration is located in exon 1 (coding exon 1) of the TMEM101 gene. This alteration results from a G to T substitution at nucleotide position 88, causing the glycine (G) at amino acid position 30 to be replaced by a cysteine (C). 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	0.17
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T;T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.1	.;N;.
REVEL	Benign	0.13
Sift	Benign	0.045	.;D;.
Sift4G	Benign	0.13	T;T;T
Polyphen		0.98	D;D;.
Vest4		0.47
MutPred		0.33		Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.40
MPC		1.3
ClinPred		0.92	D
GERP RS		5.7
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

Publications

LitVar

Other links and lift over

dbSNP: rs2049209908; hg19: chr17-42092233;