Genetic Variant TMEM234:p.Ser4Thr (chr1-32222313-A-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_019118.5(TMEM234):c.10T>A(p.Ser4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,561,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

TMEM234
NM_019118.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00200

Publications

1 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0039316416).

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.10T>A	p.Ser4Thr	missense	Exon 1 of 5	NP_061991.3
TMEM234	NM_001366191.2		c.10T>A	p.Ser4Thr	missense	Exon 1 of 6	NP_001353120.1	Q8WY98-1
TMEM234	NR_133634.2		n.41T>A		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM234	ENST00000309777.11	TSL:1 MANE Select	c.10T>A	p.Ser4Thr	missense	Exon 1 of 5	ENSP00000309792.6	Q8WY98-3
TMEM234	ENST00000373593.5	TSL:1	c.10T>A	p.Ser4Thr	missense	Exon 1 of 4	ENSP00000362695.1	Q8WY98-2
TMEM234	ENST00000344461.7	TSL:1	c.10T>A	p.Ser4Thr	missense	Exon 1 of 6	ENSP00000344021.3	Q8WY98-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000170

AC:

AN:

211144

AF XY:

0.000167

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000149

Gnomad ASJ exome

AF:

0.00452

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000205

Gnomad OTH exome

AF:

0.000199

GnomAD4 exome

AF:

0.0000880

AC:

124

AN:

1409530

Hom.:

Cov.:

AF XY:

0.0000948

AC XY:

AN XY:

696330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31564

American (AMR)

AF:

0.0000830

AC:

AN:

36152

Ashkenazi Jewish (ASJ)

AF:

0.00386

AC:

AN:

22794

East Asian (EAS)

AF:

0.00

AC:

AN:

39142

South Asian (SAS)

AF:

0.00

AC:

AN:

79128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5510

European-Non Finnish (NFE)

AF:

0.0000193

AC:

AN:

1085502

Other (OTH)

AF:

0.000207

AC:

AN:

58048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

0.000184

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.000431

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000181

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

Benign

0.074

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.55

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.090

PhyloP100

0.0020

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.090

REVEL

Benign

0.017

Sift

Benign

0.30

Sift4G

Benign

0.76

Polyphen

0.0

Vest4

0.18

MVP

0.014

MPC

0.16

ClinPred

0.036

GERP RS

-3.9

PromoterAI

0.00080

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.33

Mutation Taster

=87/13

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