Genetic Variant NM_001242313.1:c.820C>G (chr22-18530180-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001242313.1(TMEM191B):c.820C>G(p.Arg274Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 4)

Exomes 𝑓: 0.0000033 ( 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: -1.34

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10473955).

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.820C>G	p.Arg274Gly	missense	Exon 8 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.820C>G	p.Arg274Gly	missense	Exon 8 of 9	ENSP00000481358.1	P0C7N4
TMEM191B	ENST00000613577.5	TSL:3	c.850C>G	p.Arg284Gly	missense	Exon 9 of 10	ENSP00000483146.2	A0A087X073
TMEM191B	ENST00000614395.4	TSL:2	n.1495C>G		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

57466

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000333

AC:

AN:

600070

Hom.:

Cov.:

AF XY:

0.00000681

AC XY:

AN XY:

293566

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

13852

American (AMR)

AF:

0.00

AC:

AN:

5614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9360

East Asian (EAS)

AF:

0.00

AC:

AN:

11936

South Asian (SAS)

AF:

0.00

AC:

AN:

30502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2024

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

493524

Other (OTH)

AF:

0.00

AC:

AN:

23880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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;AS_VQSR

AF:

0.00

AC:

AN:

57466

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27460

African (AFR)

AF:

0.00

AC:

AN:

18308

American (AMR)

AF:

0.00

AC:

AN:

4952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1626

East Asian (EAS)

AF:

0.00

AC:

AN:

1744

South Asian (SAS)

AF:

0.00

AC:

AN:

1936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

148

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

24684

Other (OTH)

AF:

0.00

AC:

AN:

790

Alfa

AF:

0.0000843

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

Benign

0.089

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.24

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.0028

FATHMM_MKL

Benign

0.00017

LIST_S2

Benign

0.31

MetaRNN

Benign

0.10

PhyloP100

-1.3

PrimateAI

Uncertain

0.65

Sift4G

Benign

0.59

Vest4

0.071

MVP

0.16

GERP RS

-2.3

PromoterAI

0.017

Neutral

(source)

Varity_R

0.091

gMVP

0.033

Mutation Taster

=99/1

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