chr4-165085679-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001100389.2(TMEM192):​c.584G>T​(p.Arg195Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,444,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R195Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TMEM192
NM_001100389.2 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0630
Variant links:
Genes affected
TMEM192 (HGNC:26775): (transmembrane protein 192) Enables protein homodimerization activity. Located in several cellular components, including late endosome; lysosomal membrane; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08003983).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM192NM_001100389.2 linkc.584G>T p.Arg195Leu missense_variant Exon 5 of 6 ENST00000306480.11 NP_001093859.1 Q8IY95-1
TMEM192XM_011531718.4 linkc.449G>T p.Arg150Leu missense_variant Exon 4 of 5 XP_011530020.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM192ENST00000306480.11 linkc.584G>T p.Arg195Leu missense_variant Exon 5 of 6 1 NM_001100389.2 ENSP00000305069.4 Q8IY95-1
TMEM192ENST00000506087.5 linkc.572G>T p.Arg191Leu missense_variant Exon 6 of 7 2 ENSP00000425335.1 Q8IY95-2
TMEM192ENST00000505095.1 linkc.161G>T p.Arg54Leu missense_variant Exon 6 of 6 3 ENSP00000424590.1 D6RAZ6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000418
AC:
1
AN:
239382
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
129620
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000577
Gnomad SAS 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:
6.93e-7
AC:
1
AN:
1444012
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
718522
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
6.3
DANN
Benign
0.29
DEOGEN2
Benign
0.046
T;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.076
N
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.080
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M;.;.
PrimateAI
Benign
0.19
T
PROVEAN
Benign
0.19
N;N;N
REVEL
Benign
0.13
Sift
Benign
0.64
T;T;T
Sift4G
Benign
0.47
T;T;.
Polyphen
0.71
P;.;.
Vest4
0.50
MutPred
0.38
Loss of methylation at K193 (P = 0.0548);.;.;
MVP
0.040
MPC
0.034
ClinPred
0.99
D
GERP RS
0.20
Varity_R
0.027
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs553668773; hg19: chr4-166006831; COSMIC: COSV60585545; API