rs770760054

Variant names:

• chr11-8948448-C-A
• rs770760054
• NM_020644.3:c.469G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-8948448-C-A
• chr11-8948448-C-G
• chr11-8948448-C-T

Variant summary

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

The NM_020644.3(TMEM9B):​c.469G>T​(p.Asp157Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. D157N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM9B NM_020644.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.38
• Publications: 0 publications found

Genes affected

TMEM9B (HGNC:1168): (TMEM9 domain family member B) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. Predicted to be located in early endosome membrane and lysosomal membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.35357732).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020644.3. 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
	TMEM9B	NM_020644.3	MANE Select	c.469G>T	p.Asp157Tyr	missense	Exon 5 of 5	NP_065695.1	Q9NQ34-1
	TMEM9B	NM_001286094.2		c.247G>T	p.Asp83Tyr	missense	Exon 4 of 4	NP_001273023.1	Q9NQ34-2
	TMEM9B	NM_001286095.2		c.247G>T	p.Asp83Tyr	missense	Exon 5 of 5	NP_001273024.1	Q9NQ34-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM9B	ENST00000534025.6	TSL:1 MANE Select	c.469G>T	p.Asp157Tyr	missense	Exon 5 of 5	ENSP00000433361.1	Q9NQ34-1
	TMEM9B	ENST00000309134.9	TSL:1	c.247G>T	p.Asp83Tyr	missense	Exon 4 of 4	ENSP00000311842.5	Q9NQ34-2
	TMEM9B	ENST00000931334.1		c.460G>T	p.Asp154Tyr	missense	Exon 5 of 5	ENSP00000601393.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461674 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111898

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.19
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.052	T
Polyphen		0.99	D
Vest4		0.52
MutPred		0.35		Loss of disorder (P = 0.0359)
MVP		0.11
MPC		1.5
ClinPred		0.91	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.29
gMVP		0.71
Mutation Taster		=57/43	polymorphism

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: rs770760054; hg19: chr11-8969995;