Genetic Variant TMEM191B:p.Ser144Arg (chr22-18528828-C-G) – 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_001242313.1(TMEM191B):c.432C>G(p.Ser144Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00091 ( 1 hom., cov: 10)

Exomes 𝑓: 0.00015 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

TMEM191B
NM_001242313.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.19

Publications

0 publications found

Variant links:

Genes affected

TMEM191B (HGNC:33600): (transmembrane protein 191B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM191B 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=0.047846496).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242313.1. 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
	TMEM191B	NM_001242313.1	MANE Select	c.432C>G	p.Ser144Arg	missense	Exon 3 of 9	NP_001229242.1	P0C7N4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM191B	ENST00000612978.5	TSL:5 MANE Select	c.432C>G	p.Ser144Arg	missense	Exon 3 of 9	ENSP00000481358.1	P0C7N4
TMEM191B	ENST00000613577.5	TSL:3	c.432C>G	p.Ser144Arg	missense	Exon 3 of 10	ENSP00000483146.2	A0A087X073
TMEM191B	ENST00000614395.4	TSL:2	n.745C>G		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.000911

AC:

AN:

79062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000447

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:

0.000201

AC:

AN:

84384

AF XY:

0.000175

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.000195

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000151

AC:

131

AN:

868580

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

441128

show subpopulations

African (AFR)

AF:

0.00404

AC:

AN:

22772

American (AMR)

AF:

0.000293

AC:

AN:

30672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20932

East Asian (EAS)

AF:

0.00

AC:

AN:

31630

South Asian (SAS)

AF:

0.00

AC:

AN:

64056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3200

European-Non Finnish (NFE)

AF:

0.00000963

AC:

AN:

623192

Other (OTH)

AF:

0.000594

AC:

AN:

40382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.000910

AC:

AN:

79102

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

37548

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00318

AC:

AN:

21670

American (AMR)

AF:

0.000447

AC:

AN:

6710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2212

East Asian (EAS)

AF:

0.00

AC:

AN:

2312

South Asian (SAS)

AF:

0.00

AC:

AN:

2108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

182

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

38292

Other (OTH)

AF:

0.00

AC:

AN:

1068

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.340

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:

0.00244

Hom.:

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

0.60

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.0089

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.42

MetaRNN

Benign

0.048

PhyloP100

-1.2

PrimateAI

Pathogenic

0.82

Sift4G

Benign

0.17

Vest4

0.20

MVP

0.18

GERP RS

0.54

PromoterAI

-0.067

Neutral

(source)

Varity_R

0.085

gMVP

0.019

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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