Genetic Variant TMEM278:p.Arg102Cys (chr1-1427599-C-T) – 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_001146685.2(TMEM278):c.304C>T(p.Arg102Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000937 in 1,280,470 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R102S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000095 ( 0 hom., cov: 14)

Exomes 𝑓: 0.0000094 ( 0 hom. )

Consequence

TMEM278
NM_001146685.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.05

Publications

0 publications found

Variant links:

Genes affected

TMEM278 (HGNC:37099): (transmembrane protein 88B) Predicted to enable PDZ domain binding activity. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM278 links:

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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=0.229375).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146685.2. 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
	TMEM278	NM_001146685.2	MANE Select	c.304C>T	p.Arg102Cys	missense	Exon 2 of 2	NP_001140157.1	A6NKF7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM88B	ENST00000378821.4	TSL:2 MANE Select	c.304C>T	p.Arg102Cys	missense	Exon 2 of 2	ENSP00000455099.1	A6NKF7

Frequencies

GnomAD3 genomes

AF:

0.00000948

AC:

AN:

105464

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000198

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000357

AC:

AN:

56012

AF XY:

0.0000299

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000213

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:

0.00000936

AC:

AN:

1175006

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

572684

show subpopulations

African (AFR)

AF:

0.0000409

AC:

AN:

24428

American (AMR)

AF:

0.000171

AC:

AN:

17580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18712

East Asian (EAS)

AF:

0.00

AC:

AN:

26270

South Asian (SAS)

AF:

0.0000222

AC:

AN:

45008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25674

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3386

European-Non Finnish (NFE)

AF:

0.00000620

AC:

AN:

967196

Other (OTH)

AF:

0.00

AC:

AN:

46752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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:

0.00000948

AC:

AN:

105464

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

50890

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26274

American (AMR)

AF:

0.00

AC:

AN:

10820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2674

East Asian (EAS)

AF:

0.00

AC:

AN:

3398

South Asian (SAS)

AF:

0.00

AC:

AN:

2838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

50378

Other (OTH)

AF:

0.00

AC:

AN:

1376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

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

0.58

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.23

MutationAssessor

Benign

1.9

PhyloP100

-1.1

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.1

Sift

Benign

0.037

Sift4G

Benign

0.077

Polyphen

1.0

Vest4

0.18

MVP

0.65

GERP RS

1.5

Varity_R

0.11

gMVP

0.13

Mutation Taster

=97/3

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