rs766657064

Variant names:

• chr17-44012016-C-G
• rs766657064
• NM_032376.4:c.686G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-44012016-C-G
• chr17-44012016-C-T

Variant summary

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

The NM_032376.4(TMEM101):​c.686G>C​(p.Arg229Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R229Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM101 NM_032376.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM101	NM_032376.4	c.686G>C	p.Arg229Pro	missense_variant	Exon 4 of 4	ENST00000206380.8	NP_115752.1
TMEM101	NM_001304813.2	c.512G>C	p.Arg171Pro	missense_variant	Exon 5 of 5		NP_001291742.1
TMEM101	NM_001304814.2	c.512G>C	p.Arg171Pro	missense_variant	Exon 5 of 5		NP_001291743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM101	ENST00000206380.8	c.686G>C	p.Arg229Pro	missense_variant	Exon 4 of 4	1	NM_032376.4	ENSP00000206380.3
TMEM101	ENST00000589334.5	c.686G>C	p.Arg229Pro	missense_variant	Exon 5 of 5	5		ENSP00000468025.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.0086	T
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.5	.;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.015	.;D
Sift4G	Benign	0.068	T;T
Polyphen		0.61	P;P
Vest4		0.73
MutPred		0.47		Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);
MVP		0.31
MPC		0.65
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.84
gMVP		0.89

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

LitVar

Other links and lift over

dbSNP: rs766657064; hg19: chr17-42089384;