dbSNP rs575432829: TMEM92:p.Thr12Ile (chr17-50274536-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153229.3(TMEM92):c.35C>T(p.Thr12Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

TMEM92
NM_153229.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.154

Publications

1 publications found

Variant links:

Genes affected

TMEM92 (HGNC:26579): (transmembrane protein 92) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TMEM92 Gene-Disease associations (from GenCC):

nervous system disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

TMEM92 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051338434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153229.3. 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
	TMEM92	NM_153229.3	MANE Select	c.35C>T	p.Thr12Ile	missense	Exon 1 of 5	NP_694961.2	Q6UXU6
	TMEM92	NM_001168215.2		c.35C>T	p.Thr12Ile	missense	Exon 2 of 6	NP_001161687.1	Q6UXU6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM92	ENST00000507382.2	TSL:1 MANE Select	c.35C>T	p.Thr12Ile	missense	Exon 1 of 5	ENSP00000425144.1	Q6UXU6
TMEM92	ENST00000300433.7	TSL:1	c.35C>T	p.Thr12Ile	missense	Exon 2 of 6	ENSP00000300433.3	Q6UXU6
TMEM92	ENST00000918453.1		c.35C>T	p.Thr12Ile	missense	Exon 1 of 6	ENSP00000588512.1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000440

AC:

AN:

250156

AF XY:

0.0000443

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000796

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86206

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000396

AC:

AN:

1111932

Other (OTH)

AF:

0.0000828

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.0000591

AC:

AN:

152370

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41588

American (AMR)

AF:

0.000131

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

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:

0.0000494

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

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

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.35

M_CAP

Benign

0.019

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

PhyloP100

0.15

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.021

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.033

Polyphen

0.24

Vest4

0.17

MutPred

0.35

Gain of catalytic residue at L17 (P = 0.0357)

MVP

0.055

MPC

0.28

ClinPred

0.10

GERP RS

2.2

PromoterAI

0.10

Neutral

(source)

Varity_R

0.11

gMVP

0.69

Mutation Taster

=93/7

polymorphism

(source)

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

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