17-50278833-C-T

Variant summary

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

The NM_153229.3(TMEM92):​c.203C>T​(p.Ser68Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

TMEM92
NM_153229.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.212
Variant links:
Genes affected
TMEM92 (HGNC:26579): (transmembrane protein 92) Located in nucleoplasm. [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=0.07873884).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM92NM_153229.3 linkc.203C>T p.Ser68Phe missense_variant Exon 4 of 5 ENST00000507382.2 NP_694961.2 Q6UXU6
TMEM92NM_001168215.2 linkc.203C>T p.Ser68Phe missense_variant Exon 5 of 6 NP_001161687.1 Q6UXU6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM92ENST00000507382.2 linkc.203C>T p.Ser68Phe missense_variant Exon 4 of 5 1 NM_153229.3 ENSP00000425144.1 Q6UXU6
TMEM92ENST00000300433.7 linkc.203C>T p.Ser68Phe missense_variant Exon 5 of 6 1 ENSP00000300433.3 Q6UXU6
TMEM92ENST00000511882.1 linkn.299C>T non_coding_transcript_exon_variant Exon 4 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152020
Hom.:
0
Cov.:
31
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:
0.0000442
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
250656
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135500
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000529
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461150
Hom.:
0
Cov.:
32
AF XY:
0.0000344
AC XY:
25
AN XY:
726916
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000378
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152020
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000677
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.203C>T (p.S68F) alteration is located in exon 5 (coding exon 4) of the TMEM92 gene. This alteration results from a C to T substitution at nucleotide position 203, causing the serine (S) at amino acid position 68 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.049
T;T
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.49
.;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.079
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.69
N;N
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.027
Sift
Benign
0.039
D;D
Sift4G
Uncertain
0.056
T;T
Polyphen
0.0040
B;B
Vest4
0.21
MutPred
0.48
Loss of catalytic residue at S68 (P = 0.011);Loss of catalytic residue at S68 (P = 0.011);
MVP
0.076
MPC
0.42
ClinPred
0.13
T
GERP RS
1.2
Varity_R
0.099
gMVP
0.37

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

LitVar

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

Other links and lift over

dbSNP: rs760407455; hg19: chr17-48356194; API