Genetic Variant TMEM191B:p.Ser105Arg (chr22-18528577-C-G) – 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_001242313.1(TMEM191B):c.315C>G(p.Ser105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,310,010 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 0.0 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM191B
NM_001242313.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

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: 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=0.16459042).

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.315C>G	p.Ser105Arg	missense	Exon 2 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.315C>G	p.Ser105Arg	missense	Exon 2 of 9	ENSP00000481358.1	P0C7N4
TMEM191B	ENST00000613577.5	TSL:3	c.315C>G	p.Ser105Arg	missense	Exon 2 of 10	ENSP00000483146.2	A0A087X073
TMEM191B	ENST00000614395.4	TSL:2	n.494C>G		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

124188

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000160

AC:

AN:

1310010

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

645162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29712

American (AMR)

AF:

0.00

AC:

AN:

28642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23732

East Asian (EAS)

AF:

0.00

AC:

AN:

33600

South Asian (SAS)

AF:

0.00

AC:

AN:

71058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3892

European-Non Finnish (NFE)

AF:

0.0000194

AC:

AN:

1032156

Other (OTH)

AF:

0.0000184

AC:

AN:

54366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

124188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

59172

African (AFR)

AF:

0.00

AC:

AN:

33398

American (AMR)

AF:

0.00

AC:

AN:

10986

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3200

East Asian (EAS)

AF:

0.00

AC:

AN:

3224

South Asian (SAS)

AF:

0.00

AC:

AN:

3000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60314

Other (OTH)

AF:

0.00

AC:

AN:

1612

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

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

0.41

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.025

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.51

MetaRNN

Benign

0.16

PhyloP100

1.7

PrimateAI

Pathogenic

0.87

Sift4G

Uncertain

0.049

Vest4

0.14

MVP

0.16

GERP RS

0.49

PromoterAI

0.0074

Neutral

(source)

Varity_R

0.064

gMVP

0.028

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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