17-50278946-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153229.3(TMEM92):​c.316C>A​(p.Pro106Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Consequence

TMEM92
NM_153229.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.40
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0415664).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM92NM_153229.3 linkc.316C>A p.Pro106Thr missense_variant Exon 4 of 5 ENST00000507382.2 NP_694961.2 Q6UXU6
TMEM92NM_001168215.2 linkc.316C>A p.Pro106Thr 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.316C>A p.Pro106Thr missense_variant Exon 4 of 5 1 NM_153229.3 ENSP00000425144.1 Q6UXU6
TMEM92ENST00000300433.7 linkc.316C>A p.Pro106Thr missense_variant Exon 5 of 6 1 ENSP00000300433.3 Q6UXU6
TMEM92ENST00000511882.1 linkn.412C>A non_coding_transcript_exon_variant Exon 4 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152054
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
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
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250520
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135432
show subpopulations
Gnomad AFR exome
AF:
0.0000617
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152054
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.316C>A (p.P106T) alteration is located in exon 5 (coding exon 4) of the TMEM92 gene. This alteration results from a C to A substitution at nucleotide position 316, causing the proline (P) at amino acid position 106 to be replaced by a threonine (T). 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
0.081
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.21
DANN
Benign
0.78
DEOGEN2
Benign
0.0070
T;T
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.46
.;T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.042
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.039
Sift
Benign
0.42
T;T
Sift4G
Benign
0.66
T;T
Polyphen
0.56
P;P
Vest4
0.080
MutPred
0.19
Gain of glycosylation at P106 (P = 0.0142);Gain of glycosylation at P106 (P = 0.0142);
MVP
0.030
MPC
0.29
ClinPred
0.078
T
GERP RS
-2.1
Varity_R
0.067
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs1173107065; hg19: chr17-48356307; API