rs761776268

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198536.3(TMEM205):​c.39G>T​(p.Met13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

TMEM205
NM_198536.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00
Variant links:
Genes affected
TMEM205 (HGNC:29631): (transmembrane protein 205) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
CCDC159 (HGNC:26996): (coiled-coil domain containing 159)
RAB3D (HGNC:9779): (RAB3D, member RAS oncogene family) Enables myosin V binding activity. Involved in bone resorption and positive regulation of regulated secretory pathway. Located in cytoplasmic microtubule and secretory vesicle. [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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM205NM_198536.3 linkc.39G>T p.Met13Ile missense_variant Exon 1 of 3 ENST00000354882.10 NP_940938.1 Q6UW68A0A024R7D3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM205ENST00000354882.10 linkc.39G>T p.Met13Ile missense_variant Exon 1 of 3 1 NM_198536.3 ENSP00000346954.4 Q6UW68

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152120
Hom.:
0
Cov.:
32
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251366
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135880
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:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461852
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727234
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:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
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:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
21
DANN
Uncertain
0.97
DEOGEN2
Benign
0.0032
T;T;T;T;T;T;T;T;.;.;T;T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.61
.;T;.;.;.;.;.;.;T;T;T;T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.098
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.55
N;N;N;N;N;N;N;N;.;.;.;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.32
.;N;N;.;.;.;.;.;.;.;.;.
REVEL
Benign
0.022
Sift
Benign
0.30
.;T;T;.;.;.;.;.;.;.;.;.
Sift4G
Benign
0.66
T;T;T;T;T;T;T;T;.;.;T;T
Polyphen
0.0
B;B;B;B;B;B;B;B;.;.;.;.
Vest4
0.16
MutPred
0.38
Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);Gain of methylation at K12 (P = 0.0439);
MVP
0.38
MPC
0.24
ClinPred
0.33
T
GERP RS
4.1
Varity_R
0.11
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.23
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.23
Position offset: -23

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: rs761776268; hg19: chr19-11456257; API