Genetic Variant TMEM121B:p.Pro541Ser (chr22-17119507-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031890.4(TMEM121B):c.1621C>T(p.Pro541Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,575,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

TMEM121B
NM_031890.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

Publications

0 publications found

Variant links:

Genes affected

TMEM121B (HGNC:1844): (transmembrane protein 121B)

TMEM121B links:

LINC01664 (HGNC:52452): (long intergenic non-protein coding RNA 1664)

LINC01664 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.16314974).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031890.4. 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
	TMEM121B	NM_031890.4	MANE Select	c.1621C>T	p.Pro541Ser	missense	Exon 1 of 1	NP_114096.1	Q9BXQ6-1
	TMEM121B	NM_001163079.2		c.556C>T	p.Pro186Ser	missense	Exon 2 of 2	NP_001156551.1	Q9BXQ6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM121B	ENST00000331437.4	TSL:6 MANE Select	c.1621C>T	p.Pro541Ser	missense	Exon 1 of 1	ENSP00000329318.3	Q9BXQ6-1
TMEM121B	ENST00000399875.1	TSL:2	c.556C>T	p.Pro186Ser	missense	Exon 2 of 2	ENSP00000382764.1	Q9BXQ6-2
LINC01664	ENST00000846293.1		n.-12G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000550

AC:

AN:

181968

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000113

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000632

AC:

AN:

1423700

Hom.:

Cov.:

AF XY:

0.00000709

AC XY:

AN XY:

705034

show subpopulations

African (AFR)

AF:

0.0000308

AC:

AN:

32438

American (AMR)

AF:

0.00

AC:

AN:

39310

Ashkenazi Jewish (ASJ)

AF:

0.000118

AC:

AN:

25454

East Asian (EAS)

AF:

0.00

AC:

AN:

37396

South Asian (SAS)

AF:

0.0000491

AC:

AN:

81508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5592

European-Non Finnish (NFE)

AF:

9.15e-7

AC:

AN:

1093476

Other (OTH)

AF:

0.00

AC:

AN:

58918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.55

M_CAP

Benign

0.011

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

PhyloP100

2.6

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.032

Sift

Benign

0.055

Sift4G

Benign

0.38

Polyphen

0.64

Vest4

0.29

MutPred

0.26

Gain of phosphorylation at P541 (P = 0.0024)

MVP

0.21

ClinPred

0.74

GERP RS

3.2

Varity_R

0.076

gMVP

0.40

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over