Genetic Variant NM_019118.5:c.20A>G (chr1-32222015-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_019118.5(TMEM234):c.20A>G(p.Gln7Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00109 in 1,609,834 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 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

TMEM234
NM_019118.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

Publications

0 publications found

Variant links:

Genes affected

TMEM234 (HGNC:28837): (transmembrane protein 234) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM234 links:

EIF3I (HGNC:3272): (eukaryotic translation initiation factor 3 subunit I) Contributes to translation initiation factor activity. Involved in translational initiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

EIF3I links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050547034).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019118.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM234	NM_019118.5	MANE Select	c.20A>G	p.Gln7Arg	missense	Exon 2 of 5	NP_061991.3
TMEM234	NM_001366191.2		c.20A>G	p.Gln7Arg	missense	Exon 2 of 6	NP_001353120.1	Q8WY98-1
TMEM234	NR_133634.2		n.51A>G		non_coding_transcript_exon	Exon 2 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM234	ENST00000309777.11	TSL:1 MANE Select	c.20A>G	p.Gln7Arg	missense	Exon 2 of 5	ENSP00000309792.6	Q8WY98-3
TMEM234	ENST00000373593.5	TSL:1	c.20A>G	p.Gln7Arg	missense	Exon 2 of 4	ENSP00000362695.1	Q8WY98-2
TMEM234	ENST00000344461.7	TSL:1	c.20A>G	p.Gln7Arg	missense	Exon 2 of 6	ENSP00000344021.3	Q8WY98-1

Frequencies

GnomAD3 genomes

AF:

0.000782

AC:

119

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000733

AC:

177

AN:

241444

AF XY:

0.000746

show subpopulations

Gnomad AFR exome

AF:

0.000321

Gnomad AMR exome

AF:

0.000618

Gnomad ASJ exome

AF:

0.000414

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00112

AC:

1631

AN:

1457502

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

760

AN XY:

724818

show subpopulations

African (AFR)

AF:

0.000240

AC:

AN:

33384

American (AMR)

AF:

0.000631

AC:

AN:

44378

Ashkenazi Jewish (ASJ)

AF:

0.000308

AC:

AN:

25974

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.000291

AC:

AN:

85974

European-Finnish (FIN)

AF:

0.000114

AC:

AN:

52588

Middle Eastern (MID)

AF:

0.00189

AC:

AN:

4756

European-Non Finnish (NFE)

AF:

0.00133

AC:

1476

AN:

1110644

Other (OTH)

AF:

0.00118

AC:

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

196

294

392

490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

168

224

280

<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:

0.000781

AC:

119

AN:

152332

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41576

American (AMR)

AF:

0.000457

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00135

AC:

AN:

68024

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.00112

Hom.:

Bravo

AF:

0.000820

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000604

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00172

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

Uncertain

0.35

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.71

M_CAP

Benign

0.0094

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

PhyloP100

4.8

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.4

REVEL

Benign

0.058

Sift

Uncertain

0.028

Sift4G

Benign

0.21

Polyphen

0.78

Vest4

0.53

MVP

0.067

MPC

0.19

ClinPred

0.085

GERP RS

4.5

PromoterAI

0.36

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.54

Mutation Taster

=86/14

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