Genetic Variant NM_031890.4:c.1335G>C (chr22-17119793-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031890.4(TMEM121B):c.1335G>C(p.Glu445Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,583,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

TMEM121B
NM_031890.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.943

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18380216).

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.1335G>C	p.Glu445Asp	missense	Exon 1 of 1	NP_114096.1	Q9BXQ6-1
	TMEM121B	NM_001163079.2		c.270G>C	p.Glu90Asp	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.1335G>C	p.Glu445Asp	missense	Exon 1 of 1	ENSP00000329318.3	Q9BXQ6-1
TMEM121B	ENST00000399875.1	TSL:2	c.270G>C	p.Glu90Asp	missense	Exon 2 of 2	ENSP00000382764.1	Q9BXQ6-2
LINC01664	ENST00000846293.1		n.275C>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.00000507

AC:

AN:

197250

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000854

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

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:

0.00000699

AC:

AN:

1431504

Hom.:

Cov.:

AF XY:

0.00000422

AC XY:

AN XY:

711010

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33294

American (AMR)

AF:

0.0000708

AC:

AN:

42376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25760

East Asian (EAS)

AF:

0.00

AC:

AN:

39054

South Asian (SAS)

AF:

0.00

AC:

AN:

84026

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105212

Other (OTH)

AF:

0.0000335

AC:

AN:

59642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000788

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41470

American (AMR)

AF:

0.000392

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.000233

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000851

AC:

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

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.70

M_CAP

Benign

0.055

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.85

PhyloP100

0.94

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.95

Vest4

0.15

MVP

0.25

ClinPred

0.97

GERP RS

2.2

Varity_R

0.58

gMVP

0.51

Mutation Taster

=77/23

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over